157,217 results on '"*ENDOTHELIUM"'
Search Results
2. Understanding the Role of Endothelial Cells in Glioblastoma: Mechanisms and Novel Treatments.
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Hovis, Gabrielle, Chandra, Neha, Kejriwal, Nidhi, Hsieh, Kaleb, Chu, Alison, Yang, Isaac, and Wadehra, Madhuri
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angiogenesis ,endothelium ,glioblastoma ,tumor marker ,Glioblastoma ,Humans ,Endothelial Cells ,Brain Neoplasms ,Neovascularization ,Pathologic ,Animals ,Biomarkers ,Tumor - Abstract
Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.
- Published
- 2024
3. Endothelium-specific SIRT7 targeting ameliorates pulmonary hypertension through Krüpple-like factor 4 deacetylation.
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Zhang, Jin, Xu, Chenzhong, Tang, Xiaolong, Sun, Shimin, Liu, Siqi, Yang, Langmei, Chen, Yuqin, Yang, Qifeng, Wei, Tong-You, Wu, Xiaojing, Wang, Jian, Wang, Chen, Yan, Xiaosong, Yang, Lei, Niu, Yanqin, Gou, Deming, Shyy, John, and Liu, Baohua
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KLF4 ,SIRT7 ,endothelial cells ,pulmonary hypertension ,Animals ,Humans ,Mice ,Endothelium ,Vascular ,Hypertension ,Pulmonary ,Hypoxia ,Lung ,Pulmonary Artery ,Sirtuins - Abstract
AIMS: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. METHODS AND RESULTS: SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. CONCLUSION: The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy.
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- 2024
4. Hemodynamic regulation allows stable growth of microvascular networks.
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Qi, Yujia, Chang, Shyr-Shea, Wang, Yixuan, Chen, Cynthia, Baek, Kyung, Hsiai, Tzung, and Roper, Marcus
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endothelial wall ,microvessels ,optimal networks ,shear stress ,vessel adaptation ,Animals ,Mechanotransduction ,Cellular ,Zebrafish ,Microvessels ,Endothelium ,Vascular ,Veins - Abstract
How do vessels find optimal radii? Capillaries are known to adapt their radii to maintain the shear stress of blood flow at the vessel wall at a set point, yet models of adaptation purely based on average shear stress have not been able to produce complex loopy networks that resemble real microvascular systems. For narrow vessels where red blood cells travel in a single file, the shear stress on vessel endothelium peaks sharply when a red blood cell passes through. We show that stable shear-stress-based adaptation is possible if vessel shear stress set points are cued to the stress peaks. Model networks that respond to peak stresses alone can quantitatively reproduce the observed zebrafish trunk microcirculation, including its adaptive trajectory when hematocrit changes or parts of the network are amputated. Our work reveals the potential for mechanotransduction alone to generate stable hydraulically tuned microvascular networks.
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- 2024
5. Exercise mitigates flow recirculation and activates metabolic transducer SCD1 to catalyze vascular protective metabolites.
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Cavallero, Susana, Roustaei, Mehrdad, Satta, Sandro, Cho, Jae, Phan, Henry, Baek, Kyung, Blázquez-Medela, Ana, Gonzalez-Ramos, Sheila, Vu, Khoa, Park, Seul-Ki, Yokota, Tomohiro, Mack, Julia, Sigmund, Curt, Reddy, Srinivasa, Li, Rongsong, Hsiai, Tzung, and Sumner, Jennifer
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Animals ,Mice ,Aorta ,Diet ,High-Fat ,Endothelium ,Vascular ,Motor Activity ,Stearoyl-CoA Desaturase - Abstract
Exercise promotes pulsatile shear stress in the arterial circulation and ameliorates cardiometabolic diseases. However, exercise-mediated metabolic transducers for vascular protection remain under-investigated. Untargeted metabolomic analysis demonstrated that wild-type mice undergoing voluntary wheel running exercise expressed increased endothelial stearoyl-CoA desaturase 1 (SCD1) that catalyzes anti-inflammatory lipid metabolites, namely, oleic (OA) and palmitoleic acids (PA), to mitigate NF-κB-mediated inflammatory responses. In silico analysis revealed that exercise augmented time-averaged wall shear stress but mitigated flow recirculation and oscillatory shear index in the lesser curvature of the mouse aortic arch. Following exercise, endothelial Scd1-deleted mice (Ldlr-/- Scd1EC-/-) on high-fat diet developed persistent VCAM1-positive endothelium in the lesser curvature and the descending aorta, whereas SCD1 overexpression via adenovirus transfection mitigated endoplasmic reticulum stress and inflammatory biomarkers. Single-cell transcriptomics of the aorta identified Scd1-positive and Vcam1-negative endothelial subclusters interacting with other candidate genes. Thus, exercise mitigates flow recirculation and activates endothelial SCD1 to catalyze OA and PA for vascular endothelial protection.
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- 2024
6. Simvastatin restores pulmonary endothelial function in the setting of pulmonary over-circulation.
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Boehme, Jason, Sun, Xutong, Lu, Qing, Barton, Jubilee, Wu, Xiaomin, Gong, Wenhui, Datar, Sanjeev, Wang, Ting, Fineman, Jeffrey, Black, Stephen, and Raff, Gary
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Akt1 ,CTMP ,Congenital heart disease ,Endothelial dysfunction ,Endothelial nitric oxide synthase ,Nitric oxide ,Pulmonary hypertension ,Pulmonary vascular disease ,Humans ,Child ,Animals ,Sheep ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Simvastatin ,Endothelial Cells ,Nitric Oxide Synthase Type III ,Endothelium ,Vascular Diseases ,Nitric Oxide ,Endothelium ,Vascular - Abstract
Statin therapy is a cornerstone in the treatment of systemic vascular diseases. However, statins have failed to translate as therapeutics for pulmonary vascular disease. Early pulmonary vascular disease in the setting of congenital heart disease (CHD) is characterized by endothelial dysfunction, which precedes the more advanced stages of vascular remodeling. These features make CHD an ideal cohort in which to re-evaluate the potential pulmonary vascular benefits of statins, with a focus on endothelial biology. However, it is critical that the full gamut of the pleiotropic effects of statins in the endothelium are uncovered. The purpose of this investigation was to evaluate the therapeutic potential of simvastatin for children with CHD and pulmonary over-circulation, and examine mechanisms of simvastatin action on the endothelium. Our data demonstrate that daily simvastatin treatment preserves endothelial function in our shunt lamb model of pulmonary over-circulation. Further, using pulmonary arterial endothelial cells (PAECs) isolated from Shunt and control lambs, we identified a new mechanism of statin action mediated by increased expression of the endogenous Akt1 inhibitor, C-terminal modifying protein (CTMP). Increases in CTMP were able to decrease the Akt1-mediated mitochondrial redistribution of endothelial nitric oxide synthase (eNOS) which correlated with increased enzymatic coupling, identified by increases in NO generation and decreases in NOS-derived superoxide. Together our data identify a new mechanism by which simvastatin enhances NO signaling in the pulmonary endothelium and identify CTMP as a potential therapeutic target to prevent the endothelial dysfunction that occurs in children born with CHD resulting in pulmonary over-circulation.
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- 2024
7. Prospective Evaluation of the Peripheral Perfusion Index in Assessing the Organ Dysfunction and Prognosis of Adult Patients With Sepsis in the ICU.
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Guo, Qirui, Lian, Hui, Wang, Guangjian, Zhang, Hongmin, and Wang, Xiaoting
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INTENSIVE care patients , *PARTIAL thromboplastin time , *MYOCARDIAL injury , *TROPONIN I , *HOSPITAL mortality - Abstract
Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β −0.36, 95% CI −0.59 to 0.13) and activated partial thromboplastin time (APTT) (β −1.08, 95% CI −1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β −2085.48, 95% CI −3892.35 to 278.61) in univariate analysis, and with the PT (β −0.36, 95% CI −0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β −0.57, 95% CI −0.95 to 0.19), mechanical ventilation time (β −23.11, 95% CI −36.54 to 9.69), and length of ICU stay (β −1.28, 95% CI −2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Transient changes in L-arginine, asymmetric and symmetric dimethyl arginine in triathletes following Norseman Xtreme Triathlon.
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Bonnevie-Svendsen, Martin, Nyborg, Christoffer, Bratseth, Vibeke, Melau, Jørgen, and Hisdal, Jonny
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Arterial vasodilation is dependent on nitric oxide synthesized from L-arginine by endothelial nitric oxide synthase. Triathletes are reported to display altered serum concentrations of nitric oxide metabolites such as L-arginine, asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) shortly after completing long-distance triathlon races. In other populations, similar changes to nitric oxide metabolites are established risk markers of cardiovascular disease. The objective of this study was to assess serum concentrations of metabolites for endothelial nitric oxide synthesis in triathletes one week following a long-distance triathlon race. In this prospective observational study, we used high-performance liquid chromatography to measure circulating concentrations of L-arginine, ADMA, and SDMA in triathletes. Venous blood samples were collected before, immediately after, day one, and one week following the triathlon race. Serum concentrations and L-arginine/ADMA ratio were determined for each time-point and compared to baseline. L-arginine/ADMA ratio was reduced on day one (147 ± 32 vs 163 ± 40, p < 0.02). ADMA was reduced immediately after and increased at day one and remained elevated at one week (0.29 ± 0.05 mM, p < 0.001, 0.44 ± 0.08 mM, p < 0.001 and 0.42 ± 0.07 μM, p = 0.04, respectively vs 0.40 ± 0.05 μM). SDMA was increased at all time-points when compared to baseline (0.48 ± 0.10 μM, p < 0.001, 0.53 ± 0.11 μM, p < 0.001 and 0.42 ± 0.08 μM, p = 0.048 vs 0.38 ± 0.05 μM). L-arginine was only decreased immediately after (46.0 ± 9.3 μM vs. 64.6 ± 16.1 μM, p < 0.001). Long-distance triathlon racing induces altered levels of metabolites for endothelial nitric oxide production that mostly normalizes within one week following racing. The clinical relevance of these transient changes has yet to be elucidated in the athletic population. [ABSTRACT FROM AUTHOR]
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- 2024
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9. The role of Chinese herbal medicine in the regulation of oxidative stress in treating hypertension: from therapeutics to mechanisms.
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Jin, Zixuan, Lan, Yu, Li, Junying, Wang, Pengqian, and Xiong, Xingjiang
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HYPERTENSION risk factors , *DRUG therapy for hyperlipidemia , *CHINESE medicine , *RENIN-angiotensin system , *RISK assessment , *HERBAL medicine , *HYPERTENSION , *BRAIN , *BLOOD vessels , *HYPERHOMOCYSTEINEMIA , *OXIDATIVE stress , *ENDOTHELIUM , *HEART , *SYMPATHETIC nervous system , *REACTIVE oxygen species , *INSULIN resistance , *DRUG efficacy , *INFLAMMATION , *KIDNEYS , *THERAPEUTICS - Abstract
Background: Although the pathogenesis of essential hypertension is not clear, a large number of studies have shown that oxidative stress plays an important role in the occurrence and development of hypertension and target organ damage. Purpose: This paper systematically summarizes the relationship between oxidative stress and hypertension, and explores the potential mechanisms of Chinese herbal medicine (CHM) in the regulation of oxidative stress in hypertension, aiming to establish a scientific basis for the treatment of hypertension with CHM. Methods: To review the efficacy and mechanism by which CHM treat hypertension through targeting oxidative stress, data were searched from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database from their inception up to January 2024. NPs were classified and summarized by their mechanisms of action. Results: In hypertension, the oxidative stress pathway of the body is abnormally activated, and the antioxidant system is inhibited, leading to the imbalance between the oxidative and antioxidative capacity. Meanwhile, excessive production of reactive oxygen species can lead to endothelial damage and vascular dysfunction, resulting in inflammation and immune response, thereby promoting the development of hypertension and damaging the heart, brain, kidneys, blood vessels, and other target organs. Numerous studies suggested that inhibiting oxidative stress may be the potential therapeutic target for hypertension. In recent years, the clinical advantages of traditional Chinese medicine (TCM) in the treatment of hypertension have gradually attracted attention. TCM, including active ingredients of CHM, single Chinese herb, TCM classic formula and traditional Chinese patent medicine, can not only reduce blood pressure, improve clinical symptoms, but also improve oxidative stress, thus extensively affect vascular endothelium, renin–angiotensin–aldosterone system, sympathetic nervous system, target organ damage, as well as insulin resistance, hyperlipidemia, hyperhomocysteinemia and other pathological mechanisms and hypertension related risk factors. Conclusions: CHM display a beneficial multi-target, multi-component, overall and comprehensive regulation characteristics, and have potential value for clinical application in the treatment of hypertension by regulating the level of oxidative stress. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Complement, Coagulation, and Fibrinolysis: The Role of the Endothelium and Its Glycocalyx Layer in Xenotransplantation.
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Gultom, Mitra and Rieben, Robert
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VASCULAR endothelium , *GRAFT rejection , *ENDOTHELIAL cells , *GLYCOCALYX , *BLOOD coagulation - Abstract
In xenotransplantation, the vascular endothelium serves as the first point of contact between the recipient’s blood and the transplanted donor organ. The loss of the endothelium’s ability to control the plasma cascades plays a critical role in the dysregulation of the complement and coagulation systems, which greatly contribute to graft rejection and hinder long-term xenograft survival. Although it is known that an intact glycocalyx is a key feature of a resting endothelium that exhibits optimal anticoagulant and anti-inflammatory properties, the role of the endothelial glycocalyx in xenotransplantation is barely investigated so far. Here, we discuss the central role of endothelial cells and the sugar-rich endothelial glycocalyx in regulating the plasma cascades, and how the loss of these functions contributes to graft damage and rejection. We highlight the importance of preserving the regulatory functions of both endothelial cells and the glycocalyx as strategies to improve xenotransplantation outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Ultrasound assessment of endothelial dysfunction in Egyptian migraine patients.
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Elshebawy, Haidy, Mohamed Fahmy, Ebtesam, Abd El Fattah Nada, Mona, Alaa Abd El Hamid, Nouran, and Heneidy, Sarah
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CAROTID intima-media thickness ,MAGNETIC resonance imaging ,BRACHIAL artery ,VASCULAR endothelium ,MIGRAINE ,CLUSTER headache ,ENDOTHELIUM diseases - Abstract
Background : It becomes clearer that migraine is associated with vascular risks; however, preclinical vascular involvement is not sufficiently addressed. Evidences point that migraine attacks affect vascular endothelium. The aim of this study was to investigate endothelial dysfunction in migraineurs through assessment of carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) of the brachial artery and their correlation with clinical characteristics of migraine, headache severity, and brain magnetic resonance imaging (MRI) findings. Results: A statistically significant difference was found between migraineurs and controls where carotid IMT was significantly higher and FMD of the brachial artery was significantly lower in migraineurs compared to controls. Carotid IMT was significantly higher and FMD was significantly lower in chronic migraine compared to episodic migraine patients. Mean IMT values were significantly higher in patients receiving ergots and in patients with subcortical white matter lesions in brain MRI. Mean FMD values were significantly lower in patients receiving ergots. There was a significant negative correlation between FMD and carotid IMT, age of the patients, disease duration, duration of headache attacks, headache frequency, and migraine disability assessment questionnaire (MIDAS) score. There were significant positive correlations between carotid IMT and age of patients, disease duration, headache frequency, MIDAS score, and number of MRI white matter lesions. For diagnosing endothelial dysfunction in migraineurs, the sensitivity and specificity of IMT were 72.5 and 70%, respectively, with a cut-off value of 0.575 mm and that of FMD were 82.5 and 90%, respectively, with a cut-off value of 20.55%. Conclusion: Migraine coincides with endothelial dysfunction which promotes atherogenesis and increased risk of cerebral ischemia. FMD could be used as a potential biomarker for endothelial dysfunction in migraine. The affection of IMT and FMD is more in patients receiving ergots which may influence the selection of treatment in migraineurs in the future. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Visual Recovery and Endothelial Repopulation after DMEK Graft Removal and Vitrectomy for Late Endophthalmitis: A Case Report.
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Szalai, Eszter, Belin, Michael W., Szijártó, Zsuzsanna, and Csutak, Adrienne
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The aim of the study was to report a unique case with excellent clinical outcomes after late endophthalmitis following Descemet’s membrane endothelial keratoplasty (DMEK) surgery requiring donor graft removal without replacement.Introduction: A 67-year-old female with a prior ocular history of bilateral cataract surgery, Fuchs endothelial dystrophy, and pseudophakic DMEK in the left eye presented with endophthalmitis 2 months after keratoplasty. DMEK graft removal without replacement with an intracameral washout, pars plana vitrectomy, intracameral, and intravitreal antibiotics resulted in an excellent visual outcome (20/25).Case Presentation: This is a unique case of late endophthalmitis following DMEK surgery requiring graft removal and pars plana vitrectomy with excellent visual recovery without donor replacement. [ABSTRACT FROM AUTHOR]Conclusion: - Published
- 2024
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13. Vascular inflammaging: Endothelial CEACAM1 expression is upregulated by TNF‐α via independent activation of NF‐κB and β‐catenin signaling.
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Götz, Lisa, Rueckschloss, Uwe, Reimer, Andreas, Bömmel, Heike, Beilhack, Andreas, Ergün, Süleyman, and Kleefeldt, Florian
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TRANSCRIPTION factors , *ADHERENS junctions , *ENDOTHELIUM diseases , *ENDOTHELIAL cells , *CARDIOVASCULAR diseases - Abstract
Chronic inflammation with progressive age, called inflammaging, contributes to the pathogenesis of cardiovascular diseases. Previously, we have shown increased vascular expression of the Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) in aged mice and humans, presumably via mutual upregulation with the pro‐inflammatory cytokine TNF‐α. CEACAM1 is critical for aging‐associated vascular alterations like endothelial dysfunction, fibrosis, oxidative stress, and sustained inflammation and can be regarded as a main contributor to vascular inflammaging. This study was conducted to elucidate the mechanisms underlying endothelial CEACAM1 upregulation by TNF‐α in detail. Using wildtype (WT) and TNF‐α knockout (Tnf−/−) mice, we confirmed that the aging‐related upregulation of endothelial CEACAM1 critically depends on TNF‐α. The underlying mechanisms were analyzed in an endothelial cell culture model. TNF‐α time‐dependently upregulated CEACAM1 in vitro. In pharmacological experiments, we identified an early NF‐κB‐ and a delayed β‐catenin‐mediated response. Involvement of β‐catenin was further substantiated by siRNA‐mediated knockdown of the β‐catenin‐targeted transcription factor TCF4. Both signaling pathways acted independent from each other. Elucidating the delayed response, co‐immunoprecipitation analysis revealed release of β‐catenin from adherens junctions by TNF‐α. Finally, TNF‐α activated Akt kinase by increasing its Ser473 phosphorylation. Consequently, Akt kinase facilitated β‐catenin signaling by inhibiting its degradation via phosphorylation of GSK3β at Ser9 and by increased phosphorylation of β‐catenin at Ser552 that augments its transcriptional activity. Taken together, our study provides novel mechanistic insights into the aging‐related, inflammation‐mediated endothelial upregulation of CEACAM1. Beyond the pathogenesis of cardiovascular diseases, these findings may be significant to all fields of inflammaging. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Corneal Endothelial Changes in Chinese Patients with Fuchs’ Uveitis Syndrome.
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Pu, Yanlin, Zhang, Wanyun, Zhang, Xinle, Xia, Lan, and Yang, Peizeng
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PurposeMethodsResultsConclusionTo analyze the changes of corneal endothelial cells in Chinese patients with unilateral Fuchs’ uveitis syndrome (FUS) and investigate the factors relevant to these changes.Bilateral specular microscopic examination was performed in 459 Chinese patients with unilateral FUS from April 2008 to April 2023. The affected eyes constituted the study group, while the contralateral eyes served as controls.The median values of endothelial cell density (ECD), cell count, total cell size, and hexagonality were significantly lower in the FUS eyes compared to the control eyes (
p < 0.001). The median values of average cell size, maximum cell size, SD of cell size, and CV were significantly higher in the FUS eyes compared to the control eyes (p < 0.001). Central ECD showed a negative correlation with age (r = −0.339;p < 0.001), maximum IOP (r = −0.127;p = 0.006), and the interval since symptom onset (r = −0.172;p < 0.001). The ECD was lower in eyes with ocular hypertension compared to those without ocular hypertension (p < 0.001). Eyes with KPs distributed on the central corneal endothelium had a significantly lower ECD than those with KPs distributed diffusely or KPs distributed triangularly on the inferior corneal endothelium (p = 0.006).Our findings suggest decreased ECD, increased cell size, and morphological alterations in the affected eyes of Chinese patients with FUS. The reduction in ECD is correlated with age, elevated IOP, the interval since symptom onset, and the distribution of KPs. [ABSTRACT FROM AUTHOR]- Published
- 2024
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15. Vascular Perspectives of the Midfacial Superficial Musculoaponeurotic System.
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Hînganu, Delia, Hînganu, Marius Valeriu, Tamaș, Camelia, Costan, Victor Vlad, Hristian, Liliana, Negru, Dragoș, Calistru, Anca Elena, Cucu, Ramona Paula, and Lozneanu, Ludmila
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MAGNETIC resonance angiography , *VASCULAR endothelium , *NUCLEAR magnetic resonance , *CONNECTIVE tissues , *X-ray computed microtomography - Abstract
Objectives: Presently, data on the vascularization of the superficial musculoaponeurotic system of the face (SMAS) are lacking. Thus, the present study aimed to provide new conclusive data about the topography, density, and relationship of the SMAS blood vessels with other components, namely, the fibrous connective tissue and muscles. Methods: The study included a control lot of 42 cases from the archive of the radiology department. In this group, nuclear magnetic resonance angiography (MRA) was performed in order to identify the main sources of vascular supply. In the second group, tissue samples were collected from the midfacial region of 45 patients from the Oro-Maxillo-Facial and Plastic and Reconstructive Surgery clinics of 'St. Spiridon' County Clinical Emergency Hospital, Iasi. These patients received surgery for excision of tumoral formations that did not involve SMAS components. These samples underwent micro-CT analysis, hematoxylin and eosin (HE) staining, as well as immunohistochemical (IHC) staining for collagen type III, muscle tissue, and the vascular endothelium. Results: We discovered the particular way in which the SMAS components interrelate with vascularization and the regional differences between them. We have discovered a new vascular network specific to the SMAS, highlighted by both the micro-CT technique and microscopy on slides with special IHC staining. Significant differences were observed in the topographic arrangement, density, and relationships of the microscopic vasculature across midfacial regions. IHC staining provided morphological and functional information about the structure and vascularization of SMAS. Conclusions: The MRA technique could not detect the structural blood vessels of the SMAS and other methods for their in vivo visualization must be sought. The blood vessels of the SMAS mainly follow the topography of the muscle fibers. From the SMAS layer where they are found, the distribution branches reach the stroma of the region and the hypoderm. Our data can contribute to the development of surgical techniques tailored to each individual patient, as well as the enhancement of methods for stimulating cutaneous angiogenesis, improving scarring in this region, and advancing biotissue engineering techniques. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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16. Advancements in Polymer Biomaterials as Scaffolds for Corneal Endothelium Tissue Engineering.
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Wu, Kevin Y., Belaiche, Myriam, Wen, Ying, Choulakian, Mazen Y., and Tran, Simon D.
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BIOPRINTING , *DRUG delivery systems , *CORNEAL transplantation , *TISSUE engineering , *ENDOTHELIAL cells - Abstract
Corneal endothelial dysfunction is a leading cause of vision loss globally, frequently requiring corneal transplantation. However, the limited availability of donor tissues, particularly in developing countries, has spurred on the exploration of tissue engineering strategies, with a focus on polymer biomaterials as scaffolds for corneal endotlhelium regeneration. This review provides a comprehensive overview of the advancements in polymer biomaterials, focusing on their role in supporting the growth, differentiation, and functional maintenance of human corneal endothelial cells (CECs). Key properties of scaffold materials, including optical clarity, biocompatibility, biodegradability, mechanical stability, permeability, and surface wettability, are discussed in detail. The review also explores the latest innovations in micro- and nano-topological morphologies, fabrication techniques such as electrospinning and 3D/4D bioprinting, and the integration of drug delivery systems into scaffolds. Despite significant progress, challenges remain in translating these technologies to clinical applications. Future directions for research are highlighted, including the need for improved biomaterial combinations, a deeper understanding of CEC biology, and the development of scalable manufacturing processes. This review aims to serve as a resource for researchers and clinician–scientists seeking to advance the field of corneal endothelium tissue engineering. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Heparanase‐induced endothelial glycocalyx degradation exacerbates lung ischemia/reperfusion injury in male mice.
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Noda, Kentaro, Atale, Neha, Al‐Zahrani, Amer, Furukawa, Masashi, Snyder, Mark E., Ren, Xi, and Sanchez, Pablo G.
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REPERFUSION injury , *MATRIX metalloproteinases , *GENETIC regulation , *VASCULAR endothelium , *LUNG transplantation - Abstract
The endothelial glycocalyx (eGC) is a carbohydrate‐rich layer on the vascular endothelium, and its damage can lead to endothelial and organ dysfunction. Heparanase (HPSE) degrades the eGC in response to cellular stress, but its role in organ dysfunction remains unclear. This study investigates HPSE's role in lung ischemia–reperfusion (I/R) injury. A left lung hilar occlusion model was used in B6 wildtype (WT) and HPSE genetic knockout (−/−) mice to induce I/R injury in vivo. The left lungs were ischemic for 1 h followed by reperfusion for 4 h prior to investigations of lung function and eGC status. Data were compared between uninjured lungs and I/R‐injured lungs in WT and HPSE−/− mice. WT lungs showed significant functional impairment after I/R injury, whereas HPSE−/− lungs did not. Inhibition or knockout of HPSE prevented eGC damage, inflammation, and cellular migration after I/R injury by reducing matrix metalloproteinase activities. HPSE−/− mice exhibited compensatory regulation of related gene expressions. HPSE facilitates eGC degradation leading to inflammation and impaired lung function after I/R injury. HPSE may be a therapeutic target to attenuate graft damage in lung transplantation. [ABSTRACT FROM AUTHOR]
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- 2024
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18. The Crucial Triad: Endothelial Glycocalyx, Oxidative Stress, and Inflammation in Cardiac Surgery—Exploring the Molecular Connections.
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Ćurko-Cofek, Božena, Jenko, Matej, Taleska Stupica, Gordana, Batičić, Lara, Krsek, Antea, Batinac, Tanja, Ljubačev, Aleksandra, Zdravković, Marko, Knežević, Danijel, Šoštarič, Maja, and Sotošek, Vlatka
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CARDIOPULMONARY bypass , *CARDIAC surgery , *ENDOTHELIUM diseases , *OPERATIVE surgery , *OXIDATIVE stress , *GLYCOCALYX - Abstract
Since its introduction, the number of heart surgeries has risen continuously. It is a high-risk procedure, usually involving cardiopulmonary bypass, which is associated with an inflammatory reaction that can lead to perioperative and postoperative organ dysfunction. The extent of complications following cardiac surgery has been the focus of interest for several years because of their impact on patient outcomes. Recently, numerous scientific efforts have been made to uncover the complex mechanisms of interaction between inflammation, oxidative stress, and endothelial dysfunction that occur after cardiac surgery. Numerous factors, such as surgical and anesthetic techniques, hypervolemia and hypovolemia, hypothermia, and various drugs used during cardiac surgery trigger the development of systemic inflammatory response and the release of oxidative species. They affect the endothelium, especially endothelial glycocalyx (EG), a thin surface endothelial layer responsible for vascular hemostasis, its permeability and the interaction between leukocytes and endothelium. This review highlights the current knowledge of the molecular mechanisms involved in endothelial dysfunction, particularly in the degradation of EG. In addition, the major inflammatory events and oxidative stress responses that occur in cardiac surgery, their interaction with EG, and the clinical implications of these events have been summarized and discussed in detail. A better understanding of the complex molecular mechanisms underlying cardiac surgery, leading to endothelial dysfunction, is needed to improve patient management during and after surgery and to develop effective strategies to prevent adverse outcomes that complicate recovery. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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19. In Memoriam: C. Charles Michel, BA (Hons), MA, BM BCh, DPhil, FRCP, 23 March 1938−19 July 2024.
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Bates, David O., Levick, J. Rodney, and Clough, Geraldine F.
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AUTHORS - Published
- 2024
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20. A rare cause of multifocal vascular lesions and neonatal thrombocytopenia.
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Constante, Andreia Duarte, Cabral, Mafalda Félix, Carvalho, Rodrigo, Cordeiro, Ana Isabel, Afonso, Isabel, Pereira, Gabriela, and Batalha, Sara
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BLOOD platelet transfusion , *VASCULAR endothelium , *PHYSICIANS , *SYMPTOMS , *CONGENITAL disorders , *MUCOSITIS , *GASTROINTESTINAL hemorrhage - Abstract
This article provides information on a rare vascular disease called multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). MLT is characterized by the presence of multiple vascular lesions and low platelet count. The disease presents as reddish-brown skin papules and can affect various organs, including the gastrointestinal tract. Diagnosis requires a biopsy of the lesions, and treatment options are challenging and controversial. The article discusses two cases of MLT that were treated with Sirolimus, a medication that has shown promise in managing vascular anomalies. This information may be helpful for library patrons researching blood cancers and vascular anomalies. [Extracted from the article]
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- 2024
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21. Endothelial Dysfunction Does Not Occur after Acute, Elevated Homocysteine Exposure of the Lumen of the Iliac Artery of the Anaesthetised Pig.
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Markos, Farouk, O’Leary, Andrew J., Noble, Mark I.M., and Ruane-O’Hora, Therese
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VASCULAR endothelium , *ILIAC artery , *ENDOTHELIUM diseases , *SHEARING force , *HOMOCYSTEINE - Abstract
Elevated luminal homocysteine has been linked with cardiovascular disease; however, whether there is a direct effect of homocysteine on blood vessel endothelium is not clear. In this study, the acute effect of luminal homocysteine on iliac artery endothelial function was assessed in the anaesthetised pig.Introduction: Hyperhomocysteinaemic blood was injected into an occluded segment of the iliac in the anaesthetised pig for 20 min, and the effect on atrial diameter during the occlusion and during the reactive hyperaemia assessed.Methods: No significant changes in arterial diameter or pressure were observed during the incubation period at homocysteine concentrations of 10, 20, 40 and 100 µM. There was also no difference in the magnitude of the iliac diameter increase in the response to reactive hyperaemia when the incubation period was completed.Results: There is no evidence of endothelial dysfunction in response to an acute 20-min elevation in homocysteine in an intact conduit artery. [ABSTRACT FROM AUTHOR]Conclusion: - Published
- 2024
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22. The association of pre-operative biomarkers of endothelial dysfunction with the risk of post-operative neurocognitive disorders: results from the BioCog study.
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Moazzen, Sara, Janke, Jürgen, Slooter, Arjen J. C., Winterer, Georg, Spies, Claudia, Pischon, Tobias, and Feinkohl, Insa
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COGNITION disorder risk factors , *PREOPERATIVE period , *RISK assessment , *ARGININE , *RESEARCH funding , *SURGERY , *PATIENTS , *CELL adhesion molecules , *MULTIPLE regression analysis , *ENDOTHELIUM , *SURGICAL therapeutics , *DESCRIPTIVE statistics , *SURGICAL complications , *BLOOD coagulation factors , *LONGITUDINAL method , *PRE-tests & post-tests , *ODDS ratio , *ELECTIVE surgery , *DELIRIUM , *NEUROPSYCHOLOGICAL tests , *COGNITION disorders , *COMPARATIVE studies , *CONFIDENCE intervals , *FACTOR analysis , *BIOMARKERS , *PERIOPERATIVE care , *DISEASE risk factors ,PREVENTION of surgical complications - Abstract
Introduction: Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. Method: We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results: 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35–0.86). No further statistically significant results were found. Conclusion: Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Effects of Arthrospira platensis on Human Umbilical Vein Endothelial Cells.
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Krüger-Genge, Anne, Harb, Kudor, Braune, Steffen, Jung, Conrad H. G., Westphal, Sophia, Bär, Stefanie, Mauger, Olivia, Küpper, Jan-Heiner, and Jung, Friedrich
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VASCULAR endothelial cells , *CELL physiology , *ENDOTHELIAL cells , *UMBILICAL veins , *VASCULAR endothelium - Abstract
Atherosclerosis is initiated by injury or damage to the vascular endothelial cell monolayer. Therefore, the early repair of the damaged vascular endothelium by a proliferation of neighbouring endothelial cells is important to prevent atherosclerosis and thrombotic events. Arthrospira platensis (AP) has been used as a dietary supplement, mainly due to its high content of vitamins, minerals, amino acids, and pigments such as chlorophylls, carotenoids, and phycocyanin, ingredients with antioxidant, anti-inflammatory, and anti-thrombotic properties. Therefore, in this prospective, placebo-controlled, data-driven, sample-size-estimated in vitro study, we tested whether an aqueous extract of AP at different concentrations (50, 100, and 200 µg/mL) had an effect on the different cellular parameters of human umbilical vein endothelial cells. Therefore, cell impedance measurement and cell proliferation were measured to investigate the monolayer formation. In addition, cell viability, integrity, and metabolism were analysed to evaluate singular cellular functions, especially the antithrombotic state. Furthermore, cell–cell and cell–substrate interactions were observed. The highest proliferation was achieved after the addition of 100 µg/mL. This was consistently confirmed by two independent optical experiments in cell cultures 48 h and 85 h after seeding and additionally by an indirect test. At this concentration, the activation or dysfunction of HUVECs was completely prevented, as confirmed by prostacyclin and interleukin-6 levels. In conclusion, in this study, AP induced a significant increase in HUVEC proliferation without inducing an inflammatory response but altered the hemostasiological balance in favour of prostacyclin over thromboxane, thereby creating an antithrombotic state. Thus, APE could be applied in the future as an accelerator of endothelial cell proliferation after, e.g., stent placement or atherosclerosis. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Inhibitory Effects of Decursin Derivative against Lipopolysaccharide-Induced Inflammation.
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Lee, Jinhee, Heo, Jong-Beom, Cho, Sanghee, Ryu, Chang-Woo, Heo, Hae-Joon, Yun, Mi-Young, Nam, Gaewon, Song, Gyu-Yong, and Bae, Jong-Sup
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NITRIC-oxide synthases , *HEME oxygenase , *TUMOR necrosis factors , *PULMONARY artery , *ENDOTHELIAL cells - Abstract
Background: This study aims to explore the protective role of JB-V-60—a novel synthetic derivative of decur-sin—against lipopolysaccharide (LPS)-induced inflammation. Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice. Results: JB-V-60 enhanced HO-1 levels, inhibited NF-κB activation, reduced COX-2/PGE2 and iNOS/NO concentra-tions, and lowered phosphorylation of signal transducer and activator of transcription 1. It also promoted the translocation of Nrf2 into the nucleus, allowing its binding to antioxidant response elements and resulting in reduced IL-1β in LPS-stimulated HPAECs. The reduction in iNOS/NO levels by JB-V-60 was reversed when HO-1 was inhibited via RNAi. In the animal model, JB-V-60 sig-nificantly decreased iNOS expression in lung tissues and TNF-α levels in bronchoalveolar lavage fluid. Conclusions: These findings highlight the anti-inflammatory effects of JB-V-60 and its potential as a treat-ment for inflammatory disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Association of nitric oxide levels and lipid profile with endothelial dysfunction in type 2 diabetic patients.
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Algomizy, Hamza, Khan, Amjad, Smettei, Osama, Elhabiby, Mahmoud, Mustafa, Ayman Abu, and Mohieldein, Abdelmarouf
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BLOOD sugar analysis , *RISK assessment , *PREPROCEDURAL fasting , *HDL cholesterol , *NITRIC oxide , *GLYCOSYLATED hemoglobin , *LIPIDS , *ENDOTHELIUM , *DESCRIPTIVE statistics , *LDL cholesterol , *TYPE 2 diabetes , *CASE-control method , *CHOLESTEROL , *CORONARY artery disease , *TRIGLYCERIDES , *BIOMARKERS , *DISEASE risk factors , *DISEASE complications - Abstract
Background: Evidence-based screening is crucial to detect myocardial ischemia in high-risk diabetics. We explored the relationship between nitric oxide (NO) levels, lipid profile indices, and atherogenic index of plasma (AIP) in type 2 diabetics with coronary artery disease (CAD) and to determine their potential as prognostic markers. Materials and Methods: A case--control study included 50 diabetics with CAD (cases), 30 diabetics without CAD (control 1), and 23 healthy controls (control 2). Biochemical parameters were determined using standard protocols; plasma NO was measured via the Griess reaction. Results: Cases had the highest levels of NO, fasting blood sugar, glycated hemoglobin (HbA1c), and triglycerides, and the lowest total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Cases exhibited the highest TC: HDL-C, LDL-C: HDL-C, and AIP ratios. A significant positive correlation between NO and HbA1c (r = 0.328, P = 0.020). Conclusion: Chronic hyperglycemia could enhance NO overproduction driven by inducible isoform, suggesting a potential role for chronic hyperglycemia in endothelial dysfunction and vascular complications in diabetes. [ABSTRACT FROM AUTHOR]
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- 2024
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26. N‐Acetyl‐L‐Cysteine (NAC) Blunts Axitinib‐Related Adverse Effects in Preclinical Models of Glioblastoma.
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Formato, Alessia, Salbini, Maria, Orecchini, Elisa, Pellegrini, Manuela, Buccarelli, Mariachiara, Vitiani, Lucia Ricci, Giannetti, Stefano, Pallini, Roberto, D'Alessandris, Quintino Giorgio, Lauretti, Liverana, Martini, Maurizio, De Falco, Valentina, Levi, Andrea, Falchetti, Maria Laura, and Mongiardi, Maria Patrizia
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VASCULAR endothelial growth factor receptors , *STEM cell treatment , *ATAXIA telangiectasia , *RENAL cell carcinoma , *CELLULAR aging - Abstract
Objective: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH‐wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo‐angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib‐dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. Methods: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N‐Acetyl‐L‐Cysteine (NAC) might be used to reduce senescence‐associated adverse effects of axitinib treatment without altering its anti‐tumor activity. Results: We demonstrate that the use of the antioxidant molecule N‐Acetyl‐Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib‐dependent toxicity. Conclusion: Overall, we found that NAC co‐treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib‐dependent toxicity. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Formaldehyde and the transient receptor potential ankyrin-1 contribute to electronic cigarette aerosol-induced endothelial dysfunction in mice.
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Jin, Lexiao, Richardson, Andre, Lynch, Jordan, Lorkiewicz, Pawel, Srivastava, Shweta, Fryar, Laura, Miller, Alexis, Theis, Whitney, Shirk, Gregg, Bhatnagar, Aruni, Srivastava, Sanjay, Riggs, Daniel W, and Conklin, Daniel J
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ELECTRONIC cigarettes , *ENDOTHELIUM diseases , *AEROSOLS , *ANIMAL young , *CARDIOVASCULAR diseases - Abstract
Electronic nicotine delivery systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol, and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and "respiratory braking"—biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or FA (5 ppm). Short-term exposures to PG: VG and FA-induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N - 1,3-thiazolidine-4-carboxylic acid, TCA; N - 1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h). 13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0 to 3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Inflammatory, metabolic, and endothelial biomarkers before and after pregnancy complications.
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Sun, Baiyang, Gunderson, Erica P, Bertolet, Marnie, Lopa, Samia H, Bryan, Samantha G, Lewis, Cora E, and Catov, Janet M
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RISK assessment , *LEPTIN , *BODY mass index , *RESEARCH funding , *PUERPERIUM , *GESTATIONAL diabetes , *CARDIOVASCULAR diseases risk factors , *PREGNANCY outcomes , *ENDOTHELIUM , *DESCRIPTIVE statistics , *HYPERTENSION in pregnancy , *ADIPONECTIN , *ANALYSIS of variance , *PREGNANCY complications , *INFLAMMATION , *COMPARATIVE studies , *CONFIDENCE intervals , *BIOMARKERS , *C-reactive protein , *DISEASE risk factors - Abstract
Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared with those with uncomplicated births, perhaps related to prepregnancy inflammation, dysmetabolism, or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Using repeated measures analysis of variance, we estimated prepregnancy and postpregnancy biomarkers, as well as biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and term HDP groups had higher prepregnancy high-sensitivity C-reactive protein (hsCRP) (+0.37 [95% CI, 0.08-0.65]; +0.29 [95% CI, 0.04-0.55] log mg/L), higher leptin (+0.29 [95% CI, 0.09-0.50]; +0.37 [95% CI, 0.17-0.56] log ng/ml), and lower adiponectin (−0.25 [95% CI, −0.36 to −0.13); −0.11 [95% CI, −0.22 to −0.01] log ng/ml) values than those with uncomplicated births, and these profiles persisted in magnitude postpregnancy. Controlling for body mass index attenuated most profiles, except that lower prepregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower prepregnancy hsCRP and soluble intercellular adhesion molecule-1 (−0.31 [95% CI, −0.56 to −0.06] log mg/L; −0.05 [95% CI, −0.09 to −0.01] log ng/ml) and a larger leptin increase from before to after pregnancy (+0.20 [95% CI, 0.02-0.37] log ng/ml). Prepregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher body mass index. PTB may be related to adverse metabolic changes postpregnancy, although the unexpected endothelial biomarker profile warrants further study. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Endothelial Myosin IIA Is Required for the Maintenance of Blood–Brain Barrier Integrity.
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Deng, Yanan, Qiao, Ziqi, Zhou, Changping, Pei, Yujun, Xu, Han, Kang, Xuya, and Luo, Jincai
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VASCULAR endothelium , *TRANSCYTOSIS , *ISCHEMIC stroke , *INTRAVENOUS injections , *MYOSIN - Abstract
Brain endothelial cells (ECs) are essential elements of the blood–brain barrier (BBB), maintaining its integrity through both paracellular junctions and transcellular transport systems. Myosin IIA, a multifunctional protein, plays a significant role in various cellular processes, including cytoskeletal maintenance, cell division, and signal transduction. While Myosin IIA has been implicated in bleeding and ischemic stroke, its role in regulating BBB integrity under physiological conditions remains unclear. In this study, we investigated the impact of Myosin IIA deficiency on BBB integrity using intravenous tracer injections and models of epilepsy. Flow cytometry, Western blot, and real-time PCR were employed to isolate brain cells and assess changes in protein and mRNA levels. Additionally, immunofluorescence staining and electron microscopy were used to explore alterations in protein expression and the structure of BBB. Our results demonstrate that endothelial Myosin IIA deficiency increased BBB permeability and exacerbated symptoms in BBB-related diseases. Mechanistically, we found that Myosin IIA modulates β-catenin transcription and protein interactions. The overexpression of β-catenin in brain endothelial Myosin IIA deficiency mice improved BBB integrity and reduced disease severity. This study establishes Myosin IIA as a critical regulator of BBB integrity and suggests new therapeutic targets for vascular diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Exploring the Impact of Extracorporeal Membrane Oxygenation on the Endothelium: A Systematic Review.
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Li, Yakun, Volleman, Carolien, Dubelaar, Dionne P. C., Vlaar, Alexander P. J., and van den Brom, Charissa E.
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EXTRACORPOREAL membrane oxygenation , *VON Willebrand factor , *ARTIFICIAL blood circulation , *ENDOTHELIUM diseases , *EXTRACELLULAR vesicles - Abstract
Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with circulatory and/or pulmonary failure; however, the rate of complications remains high. ECMO induces systemic inflammation, which may activate and damage the endothelium, thereby causing edema and organ dysfunction. Advancing our understanding in this area is crucial for improving patient outcomes during ECMO. The goal of this review is to summarize the current evidence of the effects of ECMO on endothelial activation and damage in both animals and patients. PubMed and Embase databases were systematically searched for both clinical and animal studies including ECMO support. The outcome parameters were markers of endothelial activation and damage or (in)direct measurements of endothelial permeability, fluid leakage and edema. In total, 26 studies (patient n = 16, animal n = 10) fulfilled all eligibility criteria, and used VA-ECMO (n = 13) or VV-ECMO (n = 6), or remained undefined (n = 7). The most frequently studied endothelial activation markers were adhesion molecules (ICAM-1) and selectins (E- and P-selectin). The levels of endothelial activation markers were comparable to or higher than in healthy controls. Compared to pre-ECMO or non-ECMO, the majority of studies showed stable or decreased levels. Angiopoietin-2, von Willebrand Factor and extracellular vesicles were the most widely studied circulating markers of endothelial damage. More than half of the included studies showed increased levels when compared to normal ranges, and pre-ECMO or non-ECMO values. In healthy animals, ECMO itself leads to vascular leakage and edema. The effect of ECMO support in critically ill animals showed contradicting results. ECMO support (further) induces endothelial damage, but endothelial activation does not, in the critically ill. Further research is necessary to conclude on the effect of the underlying comorbidity and type of ECMO support applied on endothelial dysfunction. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Integrating molecular and cellular components of endothelial shear stress mechanotransduction.
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Power, Gavin, Ferreira-Santos, Larissa, Martinez-Lemus, Luis A., and Padilla, Jaume
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SHEARING force , *CELL anatomy , *LIPID rafts , *TYPE 2 diabetes , *MEMBRANE lipids - Abstract
The lining of blood vessels is constantly exposed to mechanical forces exerted by blood flow against the endothelium. Endothelial cells detect these tangential forces (i.e., shear stress), initiating a host of intracellular signaling cascades that regulate vascular physiology. Thus, vascular health is tethered to the endothelial cells' capacity to transduce shear stress. Indeed, the mechanotransduction of shear stress underlies a variety of cardiovascular benefits, including some of those associated with increased physical activity. However, endothelial mechanotransduction is impaired in aging and disease states such as obesity and type 2 diabetes, precipitating the development of vascular disease. Understanding endothelial mechanotransduction of shear stress, and the molecular and cellular mechanisms by which this process becomes defective, is critical for the identification and development of novel therapeutic targets against cardiovascular disease. In this review, we detail the primary mechanosensitive structures that have been implicated in detecting shear stress, including junctional proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1), the extracellular glycocalyx and its components, and ion channels such as piezo1. We delineate which molecules are truly mechanosensitive and which may simply be indispensable for the downstream transmission of force. Furthermore, we discuss how these mechanosensors interact with other cellular structures, such as the cytoskeleton and membrane lipid rafts, which are implicated in translating shear forces to biochemical signals. Based on findings to date, we also seek to integrate these cellular and molecular mechanisms with a view of deciphering endothelial mechanotransduction of shear stress, a tenet of vascular physiology. [ABSTRACT FROM AUTHOR]
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- 2024
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32. The vascular influence of melatonin on endothelial response to angiotensin II in diabetic rat aorta.
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Mahmood, Nazar M.Shareef, Mahmud, Almas MR, and Maulood, Ismail M
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ACE inhibitors , *STREPTOZOTOCIN , *ENDOTHELIUM diseases , *CONDITIONED response , *MELATONIN , *ANGIOTENSIN converting enzyme , *ENDOTHELIUM - Abstract
The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE2), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE2 inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE2 inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE2 inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE2 inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis.
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Girardis, Massimo, David, Sascha, Ferrer, Ricard, Helms, Julie, Juffermans, Nicole P., Martin-Loeches, Ignacio, Povoa, Pedro, Russell, Lene, Shankar-Hari, Manu, Iba, Toshiaki, Coloretti, Irene, Parchim, Nicholas, and Nielsen, Nathan D.
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ENDOTHELIUM diseases , *BLOOD coagulation , *OVERALL survival , *SEPSIS , *CRITICALLY ill - Abstract
The interplay between the immune system, coagulation, and endothelium is critical in regulating the host response to infection. However, in sepsis and other critical illnesses, a dysregulated immune response can lead to excessive alterations in these mechanisms, resulting in coagulopathy, endothelial dysfunction, and multi-organ dysfunction. This review aims to provide a comprehensive analysis of the pathophysiological mechanisms that govern the complex interplay between immune dysfunction, endothelial dysfunction, and coagulation in sepsis. It emphasises clinical significance, evaluation methods, and potential therapeutic interventions. Understanding these mechanisms is essential for developing effective treatments that can modulate the immune response, mitigate thrombosis, restore endothelial function, and ultimately improve patient survival. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Long non-coding RNA H19X as a regulator of mononuclear cell adhesion to the endothelium in systemic sclerosis.
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Tirelli, Francesca, Pachera, Elena, Gmür, Sabrina, Lafyatis, Robert, Huang, Mengqi, Zulian, Francesco, Retamosa, Eva Camarillo, Kania, Gabriela, and Distler, Oliver
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STATISTICAL hypothesis testing , *DATA analysis , *ENZYME-linked immunosorbent assay , *ENDOTHELIUM , *MANN Whitney U Test , *RNA , *GENE expression , *SYSTEMIC scleroderma , *ENDOTHELIAL cells , *WESTERN immunoblotting , *CYTOKINES , *VASCULAR cell adhesion molecule-1 - Abstract
Objective To define the functional relevance of H19 X-linked (H19X) co-expressed long non-coding RNA (lncRNA) in endothelial cell (EC) activation as a key process in SSc vasculopathy. Methods H19X expression in SSc skin biopsies was analysed from single-cell RNA sequencing (scRNA-seq) data. Differential expression and pathway enrichment analysis between cells expressing (H19Xpos) and non-expressing H19X (H19Xneg) cells was performed. H19X function was investigated in human dermal microvascular ECs (HDMECs) by silencing. H19X and EC adhesion molecule levels were analysed by real-time quantitative PCR and western blot after stimulation with pro-inflammatory cytokines. Cytoskeletal rearrangements were analysed by fluorescent staining. Endothelial adhesion was evaluated by co-culture of HDMECs and fluorescent-labelled peripheral blood mononuclear cells (PBMCs). Shedding vascular cell adhesion protein 1 (VCAM1) was evaluated by ELISA on HDMEC supernatant. Results The scRNA-seq data showed significant upregulation of H19X in SSc compared with healthy ECs. In HDMECs, H19X was consistently induced by IFN type I and II. H19X knockdown lead to a significant decrease in the mRNA of several adhesion molecules. In particular, VCAM1 was significantly reduced at the protein and mRNA levels. Co-expression analysis of the scRNA-seq data confirmed higher expression of VCAM1 in H19Xpos ECs. ECs were also strongly associated with the 'cell adhesion molecule' pathway. Moreover, the VCAM1 downstream pathway displayed less activation following H19X knockdown. Contractility of HDMECs, PBMC adhesion to HDMECs and VCAM1 shedding were also reduced following H19X knockdown. Conclusions lncRNA H19X may contribute to EC activation in SSc vasculopathy, acting as a regulator of expression of adhesion molecules in ECs. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.
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Liu, Yang, Zhou, Miao, Cheng, Hao, and Du, Jing
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COMBINATION drug therapy , *PROTEINS , *SUPEROXIDE dismutase , *PROTEINURIA , *LOW-molecular-weight heparin , *MAGNESIUM sulfate , *NITRIC oxide , *PATIENT safety , *RESEARCH funding , *STATISTICAL sampling , *PROTHROMBIN time , *ENDOTHELIUM , *PREGNANCY outcomes , *TREATMENT effectiveness , *PREGNANT women , *RANDOMIZED controlled trials , *DESCRIPTIVE statistics , *FIBRIN fibrinogen degradation products , *OXIDATIVE stress , *LDL cholesterol , *ENOXAPARIN , *PARTIAL thromboplastin time , *LIPID peroxidation (Biology) , *HYPERTENSION in pregnancy , *AGE factors in disease , *PREECLAMPSIA , *LABETALOL , *ENDOTHELIAL cells , *DIASTOLIC blood pressure , *URINALYSIS , *FIBRINOGEN , *BLOOD coagulation , *COMPARATIVE studies , *SYSTOLIC blood pressure , *MALONDIALDEHYDE - Abstract
Objective: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Methods: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. Results: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. Conclusion: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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36. Alteration of Piezo1 signaling in type 2 diabetic mice: focus on endothelium and BKCa channel.
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Haam, Chae Eun, Choi, Sooyeon, Byeon, Seonhee, Oh, Eun Yi, Choi, Soo-Kyoung, and Lee, Young-Ho
- Subjects
- *
WESTERN immunoblotting , *TYPE 2 diabetes , *VASCULAR resistance , *PROTEIN expression , *MESENTERIC artery , *VASCULAR diseases , *ENDOTHELIUM , *ION channels , *POTASSIUM channels - Abstract
Piezo1 mechanosensitive ion channel plays a important role in vascular physiology and disease. This study aimed to elucidate the altered signaling elicited by Piezo1 activation in the arteries of type 2 diabetes. Ten- to 12-week-old male C57BL/6 (control) and type 2 diabetic mice (db−/db−) were used. The second-order mesenteric arteries (~ 150 μm) were used for isometric tension experiments. Western blot analysis and immunofluorescence staining were performed to observe protein expression. Piezo1 was significantly decreased in mesenteric arteries of type 2 diabetic mice compared to control mice, as analyzed by western blot and immunofluorescence staining. Piezo1 agonist, Yoda1, concentration-dependently induced relaxation of mesenteric arteries in both groups. Interestingly, the relaxation response was significantly greater in control mice than in db−/db− mice. The removal of endothelium reduced relaxation responses induced by Yoda1, which was greater in control mice than db−/db− mice. Furthermore, the relaxation response was reduced by pre-treatment with various types of K+ channel blockers in endothelium-intact arteries in control mice. In endothelium-denuded arteries, pre-incubation with charybdotoxin, an Ca2+-activated K+ channel (BKCa channel) blocker, significantly attenuated Yoda1-induced relaxation in db−/db− mice, while there was no effect in control mice. Co-immunofluorescence staining showed co-localization of Piezo1 and BKCa channel was more pronounced in db−/db− mice than in control mice. These results indicate that the vascular responses induced by Piezo1 activation are different in the mesenteric resistance arteries in type 2 diabetic mice. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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37. Vascular endothelium: The interface for multiplex signal transduction.
- Author
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Cheng, Chak Kwong and Huang, Yu
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CELLULAR signal transduction , *VASCULAR endothelium , *HEART metabolism disorders , *SHEARING force , *CARDIOVASCULAR diseases - Abstract
As the innermost monolayer of the vasculature, endothelial cells (ECs) serve as the interface for multiplex signal transduction. Directly exposed to blood-borne factors, both endogenous and exogenous, ECs actively mediate vascular homeostasis and represent a therapeutic target against cardiometabolic diseases. ECs act as the first-line gateway between gut-derived substances and vasculature. Additionally, ECs convert blood flow-exerted hemodynamic forces into downstream biochemical signaling to modulate vascular pathophysiology. Besides, ECs can sense other forms of stimuli, like cell extrusion, thermal stimulation, photostimulation, radiation, magnetic field, noise, and gravity. Future efforts are still needed to deepen our understanding on endothelial biology. [Display omitted] • ECs are interfaces for multiplex signal transduction in the vasculature. • ECs are gatekeepers between gut-derived substances and vasculature. • ECs convert hemodynamic forces to biochemical signals, mediating vasopathology. • ECs are sensitive to various environmental stimuli. [ABSTRACT FROM AUTHOR]
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- 2024
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38. The Impact of Enteral Nimodipine on Endothelial Cell Apoptosis in an Animal Subarachnoid Hemorrhage Model.
- Author
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Cho, Young Dae, Byoun, Hyoung Soo, Park, Kwang Hyon, Won, Young Il, and Lim, Jeongwook
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- *
BASILAR artery , *CARDIOVASCULAR system , *SUBARACHNOID hemorrhage , *BRAIN stem , *CEREBRAL ischemia - Abstract
Background: Enteral nimodipine is the most evidence-based and widely used drug for the treatment of delayed cerebral ischemia and is known to have various neuroprotective functions. However, the neuroprotective mechanism of nimodipine still remains unclear, and the effects of nimodipine remain ambiguous. Herein, we studied the effect of enteral nimodipine on endothelial apoptosis after subarachnoid hemorrhage (SAH). Methods: SAH was experimentally introduced in white rabbits (n = 42) that were grouped as follows: enteral nimodipine (SAH-nimodipine group, n = 14), a control that received normal saline (SAH-saline group, n = 13), and a control without hemorrhage (control group, n = 15). On the third day after SAH induction, the brain stem, including the vertebrobasilar vascular system, was extracted. The effects of enteral nimodipine were analyzed by group using histopathologic analysis, including immunohistochemical staining of apoptosis-related proteins (Bcl2 [anti-apoptotic] and Bax [pro-apoptotic]). Results: Cytoplasmic vacuolation of smooth muscle cells was observed in two SAH hemorrhagic groups and was more prominent in the SAH-saline group. Endothelial desquamation was observed only in the SAH-saline group. For the basilar artery, expression of Bcl2 and Bax in the SAH-nimodipine group was lower than that in the SAH-saline group, but significant differences were not observed (pBcl2 = 0.311 and pBax = 0.720, respectively). In penetrated arterioles, the expression of Bax in the SAH-nimodipine group was significantly lower than that of the SAH-saline group (p < 0.001). The thickness of the tunica media in the basilar artery was thinner in the SAH-nimodipine group than in the SAH-saline group (p < 0.001). Conclusions: This study suggests that enteral nimodipine may have a neuroprotective function by inhibiting endothelial apoptosis in small arterioles and preventing smooth muscle cell proliferation in large arteries. [ABSTRACT FROM AUTHOR]
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- 2024
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39. Common variable immunodeficiency disorder (CVID)-related liver disease: assessment of the main histological aspects using novel semiquantitative scoring systems, image analysis and correlation with clinical parameters of liver stiffness and portal hypertension
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Silva, Hiroshi, Xavier de Brito, Camila Gabriela, Hall, Andrew, Eden, Nadia, Somers, Henry, Burke, Niall, Burns, Siobhan O., Lowe, David, Thorburn, Douglas, Halliday, Neil, and Quaglia, Alberto
- Subjects
COMMON variable immunodeficiency ,CYTOTOXIC T cells ,CROHN'S disease ,AGAMMAGLOBULINEMIA ,HEPATIC fibrosis ,LUNGS ,LIVER regeneration ,ENDOTHELIUM ,ROOT-tubercles - Published
- 2024
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40. A prospective study on varicose veins surgery impact on systemic endothelial function evaluated by arterial brachial flow mediated dilation.
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Nóbrega, Leandro, Cardoso, Rita, Leite-Moreira, Adelino, and Castro-Ferreira, Ricardo
- Abstract
Objectives: Chronic venous disease (CVD) is a prevalent pathology, and endothelial dysfunction is recognized as a core of its physiopathology. Flow-mediated dilation (FMD) is one of the most widely used tests for evaluating endothelial function. The aim of this study is to evaluate the influence of varicose vein (VV) surgery on FMD. Methods: A prospective study with patients with superficial CVD and saphenous incompetence on Doppler ultrasonography that were proposed for VV surgery. The FMD test was performed before and 6 months after the procedure. The operator performing the post-operative evaluation was blinded to the pre-operative result. Results: A total of 42 patients were included in the analysis. The median pre-operative percent change of FMD was 4.20% (±1.30) and the post-operative was 4.56% (±1.25) (p = 0.819). Conclusions: Our findings do not corroborate the presence of an overall endothelial dysfunction prone to modulation by surgery. Nevertheless, further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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41. Pulmonary fibrosis: pathogenesis and therapeutic strategies.
- Author
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Wang, Jianhai, Li, Kuan, Hao, De, Li, Xue, Zhu, Yu, Yu, Hongzhi, and Chen, Huaiyong
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PULMONARY fibrosis ,CELLULAR aging ,CELL physiology ,LUNG diseases ,ENVIRONMENTAL exposure - Abstract
Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate and function and excessive accumulation of extracellular matrix, leading to lung tissue scarring and impaired respiratory function. Although our understanding of its pathogenesis has increased, effective treatments remain scarce, and fibrotic progression is a major cause of mortality. Recent research has identified various etiological factors, including genetic predispositions, environmental exposures, and lifestyle factors, which contribute to the onset and progression of PF. Nonetheless, the precise mechanisms by which these factors interact to drive fibrosis are not yet fully elucidated. This review thoroughly examines the diverse etiological factors, cellular and molecular mechanisms, and key signaling pathways involved in PF, such as TGF‐β, WNT/β‐catenin, and PI3K/Akt/mTOR. It also discusses current therapeutic strategies, including antifibrotic agents like pirfenidone and nintedanib, and explores emerging treatments targeting fibrosis and cellular senescence. Emphasizing the need for omni‐target approaches to overcome the limitations of current therapies, this review integrates recent findings to enhance our understanding of PF and contribute to the development of more effective prevention and management strategies, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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42. Laminin Beta 2 Is Localized at the Sites of Blood–Brain Barrier and Its Disruption Is Associated With Increased Vascular Permeability, Histochemical, and Transcriptomic Study.
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Bannykh, Katherine S., Fuentes-Fayos, Antonio C., Linesch, Paul W., Breunig, Joshua J., and Bannykh, Serguei I.
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EXTRACELLULAR matrix proteins ,VASCULAR endothelial growth factors ,MAGNETIC resonance imaging ,ENDOTHELIAL cells ,LAMININS ,PERICYTES - Abstract
Heterotrimeric extracellular matrix proteins laminins are mostly deposited at basal membranes and are important in repair and neoplasia. Here, we localize laminin beta 2 (LAMB2) at the sites of blood–brain barrier (BBB). Microvasculature (MV) of normal brain is endowed with complete LAMB2 coverage. In contrast, its cognate protein laminin beta 1 (LAMB1) is absent in MV of normal brain but emerges at the sprouting tip of a growing vessels. Similarly, vascular proliferation in high-grade gliomas (HGG) is accompanied by marked overexpression of LAMB1, whereas LAMB2 shows deficient deposition. We find that many brain pathologies with presence of post-gadolinium enhancement (PGE) on magnetic resonance imaging (MRI) show disruption of LAMB2 vascular ensheathment. Inhibition of vascular endothelial growth factor signaling in HGG blocks angiogenesis, suppresses PGE in HGG, prevents expression of LAMB1, and restores LAMB2 vascular coverage. Analysis of single-cell RNA sequencing (scRNA-seq) databases shows that in quiescent brain LAMB2 is predominantly expressed by BBB-associated pericytes (PCs) and endothelial cells (ECs), whereas neither cell types produce LAMB1. In contrast, in HGG, both LAMB1 and 2 are overexpressed by endothelial precursor cells, a phenotypically unique immature group, specific to proliferating hyperplastic MV. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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43. Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.
- Author
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Hough, Rebecca F., Alvira, Cristina M., Bastarache, Julie A., Erzurum, Serpil C., Kuebler, Wolfgang M., Schmidt, Eric P., Shimoda, Larissa A., Abman, Steven H., Alvarez, Diego F., Belvitch, Patrick, Bhattacharya, Jahar, Birukov, Konstantin G., Chan, Stephen Y., Cornfield, David N., Dudek, Steven M., Garcia, Joe G. N., Harrington, Elizabeth O., Hsia, Connie C. W., Islam, Mohammad Naimul, and Jonigk, Danny D.
- Subjects
ENDOTHELIUM diseases ,PUBLIC health officers ,ENDOTHELIAL cells ,GENETIC translation ,CELL physiology ,ENDOTHELIUM - Abstract
Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis. Although our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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44. Associations between endothelial cell characteristics and corneal topography findings in different stages of keratoconus.
- Author
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Reyhan, Ali Hakim, Karadağ, Ayşe Sevgi, and Şimşek, Ali
- Abstract
Purpose: This study aimed to compare and correlate specular microscope indices and corneal topography indices in different stages of keratoconus. Methods: Two hundred forty-six eyes of 123 participants were enrolled in the study. Corneal topography was performed using Sirius (CSO, Italy), with a rotating Scheimpflug camera and a Placido disc topographer. Corneal endothelial cell indices were assessed using a specular microscope (Nidek CEM-530, Japan). Eyes were graded as keratoconus stages 0–4 according to the Amsler-Krumeich classification. Corneal topography and endothelial cell indices were compared among the groups, and the correlations between them were analyzed. Results: The mean age of the patients was 23.26 ± 6.75 years (range, 14–47 years). Forty-eight cases were male (39%) and 75 were female (61%). There were no statistically significant age (p = 0.578) or sex ratio (p = 0.529) differences between the groups. Twenty-nine eyes were included in the control group (11.78%), while 41 (16.67%) had stage 1 keratoconus, 88 (35.77%) had stage 2, and 88 (35.77%) had stage 3. Measurement was not possible in stage 4 keratoconus. No statistically significant difference was determined in specular microscopy values according to the stage of keratoconus, except for the number of analyzed cells (NUM) (p > 0.05). The lowest NUM values were observed in stages 1, 2, and 3, with values of 184.34 ± 67.62 cells/mm
2 , 155.07 ± 59.48 cells/mm2 , and 127.06 ± 64.39 cells/mm2 , respectively (p = 0.001). In the keratoconus group, weak statistically significant negative correlations were observed between NUM and SimK1, SimK2, KVf, BCVf, KVb, and BCVb, while a weak positive correlation was noted between NUM and central corneal thickness (p < 0.05). Conclusions: NUM seems to decrease, while endothelial cell density exhibits no significant changes, with the progression of keratoconus. It appears that as keratoconus index values increase, NUM may decrease in different stages of keratoconus. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
45. Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.
- Author
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Buncha, Vadym, Fopiano, Katie Anne, Lang, Liwei, Ilatovskaya, Daria V., Verin, Alexander, and Bagi, Zsolt
- Subjects
VASCULAR endothelium ,PHOSPHODIESTERASE inhibitors ,OLDER people ,VASCULAR resistance ,HEART metabolism disorders - Abstract
As individuals age, there is a gradual decline in cardiopulmonary function, often accompanied by cardiac pump dysfunction leading to increased pulmonary vascular resistance (PVR). Our study aims to investigate the changes in cardiac and pulmonary vascular function associated with aging. Additionally, we aim to explore the impact of phosphodiesterase 9A (PDE9A) inhibition, which has shown promise in treating cardiometabolic diseases, on addressing left ventricle (LV) dysfunction and elevated PVR in aging individuals. Young (3 months old) and aged (32 months old) male C57BL/6 mice were used. Aged mice were treated with the selective PDE9A inhibitor PF04447943 (1 mg/kg/day) through intraperitoneal injections for 10 days. LV function was evaluated using cardiac ultrasound, and PVR was assessed in isolated, ventilated lungs perfused under a constant flow condition. Additionally, changes in PVR were measured in response to perfusion of the endothelium-dependent agonist bradykinin or to nitric oxide (NO) donor sodium nitroprusside (SNP). PDE9A protein expression was measured by Western blots. Our results demonstrate the development of LV diastolic dysfunction and increased PVR in aged mice. The aged mice exhibited diminished decreases in PVR in response to both bradykinin and SNP compared to the young mice. Moreover, the lungs of aged mice showed an increase in PDE9A protein expression. Treatment of aged mice with PF04447943 had no significant effect on LV systolic or diastolic function. However, PF04447943 treatment normalized PVR and SNP-induced responses, though it did not affect the bradykinin response. These data demonstrate a development of LV diastolic dysfunction and increase in PVR in aged mice. We propose that inhibitors of PDE9A could represent a novel therapeutic approach to specifically prevent aging-related pulmonary dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Single‐cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease.
- Author
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Chandler, Jennifer C, Jafree, Daniyal J, Malik, Saif, Pomeranz, Gideon, Ball, Mary, Kolatsi‐Joannou, Maria, Piapi, Alice, Mason, William J, Benest, Andrew V, Bates, David O, Letunovska, Aleksandra, Al‐Saadi, Reem, Rabant, Marion, Boyer, Olivia, Pritchard‐Jones, Kathy, Winyard, Paul J, Mason, Andrew S, Woolf, Adrian S, Waters, Aoife M, and Long, David A
- Subjects
TRANSCRIPTION factors ,KIDNEY glomerulus diseases ,ENDOTHELIAL cells ,JUVENILE diseases ,ADRENOMEDULLIN - Abstract
WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell‐types in the glomerulus. We hypothesised that this could be resolved using single‐cell RNA sequencing (scRNA‐seq) and ligand‐receptor analysis to profile glomerular cell–cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (Wt1R394W/+). Podocytes were the most dysregulated cell‐type in the early stages of Wt1R394W/+ disease, with disrupted angiogenic signalling between podocytes and the endothelium, including the significant downregulation of transcripts for the vascular factors Vegfa and Nrp1. These signalling changes preceded glomerular endothelial cell loss in advancing disease, a feature also observed in biopsy samples from human WT1 glomerulopathies. Addition of conditioned medium from murine Wt1R394W/+ primary podocytes to wild‐type glomerular endothelial cells resulted in impaired endothelial looping and reduced vascular complexity. Despite the loss of key angiogenic molecules in Wt1R394W/+ podocytes, the pro‐vascular molecule adrenomedullin was upregulated in Wt1R394W/+ podocytes and plasma and its further administration was able to rescue the impaired looping observed when glomerular endothelium was exposed to Wt1R394W/+ podocyte medium. In comparative analyses, adrenomedullin upregulation was part of a common injury signature across multiple murine and human glomerular disease datasets, whilst other gene changes were unique to WT1 disease. Collectively, our study describes a novel role for altered angiogenic signalling in the initiation of WT1 glomerulopathy. We also identify adrenomedullin as a proangiogenic factor, which despite being upregulated in early injury, offers an insufficient protective response due to the wider milieu of dampened vascular signalling that results in endothelial cell loss in later disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Sodium Selenite Ameliorates Silver Nanoparticles Induced Vascular Endothelial Cytotoxic Injury by Antioxidative Properties and Suppressing Inflammation Through Activating the Nrf2 Signaling Pathway.
- Author
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Ma, Yunyun, Wang, Lei, He, Jing, Ma, Xueping, Wang, Jingjing, Yan, Ru, Ma, Wanrui, Ma, Huiyan, Liu, Yajuan, Sun, Hongqian, Zhang, Xiaoxia, Jia, Shaobin, and Wang, Hao
- Abstract
Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications. Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
48. The crossroad between tumor and endothelial cells.
- Author
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Ribatti, Domenico
- Subjects
- *
ENDOTHELIAL cells , *TUMOR growth , *ANTIGEN presentation , *TUMOR microenvironment , *ENDOTHELIUM - Abstract
Endothelial cells are critical in tumor development, and the specific targeting of endothelial cells offers a potent means to effectively impede angiogenesis and suppress the growth of tumors. Tumor endothelial cells are responsible for the loss of anticancer immunity, the so-called endothelial anergy, i.e., the unresponsiveness of tumor endothelial cells to pro-inflammatory stimulation, not allowing adhesion of immune cells to the endothelium. Endothelial cells downregulate antigen presentation and recruitment of immune cells, contributing to immunosuppression. Targeting endothelial cells may assist in improving the immune effect of immune cells in tumor microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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49. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker of stage III-IV, grade C periodontitis through the impact of post-radiotherapy on head and neck cancer patients.
- Author
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Al-Kubaisi, Ahmed A., Ghazi, Maysam Abdulrahman, Majeed, Nisreen Salah, Aldelaimi, Ekram R., and Enezei, Hamid H.
- Subjects
CHRONIC disease diagnosis ,LEUCOCYTES ,PEARSON correlation (Statistics) ,RADIOTHERAPY ,RECEIVER operating characteristic curves ,HOMEOSTASIS ,HEAD & neck cancer ,ENZYME-linked immunosorbent assay ,PERIODONTAL disease ,GINGIVITIS ,KRUSKAL-Wallis Test ,CANCER patients ,XEROSTOMIA ,ENDOTHELIUM ,MANN Whitney U Test ,DESCRIPTIVE statistics ,CHRONIC diseases ,PERIODONTAL pockets ,PERIODONTICS ,DENTAL plaque ,DATA analysis software ,PERIODONTITIS ,BIOMARKERS ,CELL receptors - Abstract
Background: The urokinase-type plasminogen activator receptor (uPAR) plays an essential function in leukocytes and endothelial homeostasis and, therefore, in the development of chronic periodontitis. Methods: The study enrolled 150 participants, 50 chronic periodontitis with head and neck cancer post radiotherapy (CP + HNC post-RT) patients, 50 chronic periodontitis (CP) without HNC patients, and 50 healthy controls. Clinical Attachment Loss (CAL), Probing Pocket Depth (PPD), Plaque Index (PI), and Gingival Bleeding Index (GBI) were recorded. An enzyme-linked immunosorbent assay (ELISA) was constructed to quantify serum (suPAR) levels. Results: Stage and grade of periodontitis were stage III-IV, grade C in patients (CP + HNC post-RT), stage I-III, grade A/B in patients (CP without HNC), and absent in (healthy). Chronic periodontitis with HNC post-RT patients presented a significantly higher proportion of suPAR levels (506.7 pg/ml) compared to chronic periodontitis without HNC and healthy controls (423.08 pg/ml and 255.9 pg/ml), respectively. A significant positive correlation was found between serum suPAR levels and CAL, PPD, PI, and GBI in the periodontal disease groups. ROC results of suPAR (AUC = 0.976 for CP + HNC post-RT, AUC = 0.872 for CP without HNC). Hyposalivation appeared in patients (CP + HNC post-RT; 0.15 [0.11–0.23] ml/min, P = 0.001) and (CP without HNC; 0.30 [0.25–0.41] ml/min, P = 0.001), compared to healthy controls; 0.35 [0.28–0.54] ml/min, P = 0.001). Conclusion: The study showed a significant elevation in serum suPAR levels in CP + HNC post-RT patients compared to the CP without HNC and control groups. Clinical trial registration: The study was registered retrospectively; clinicaltrials.gov identifier: NCT06529588. Date of registration: July 31, 2024 https://clinicaltrials.gov/study/NCT06529588. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. Comprehensive assessment of corneal microstructural changes following V4c implantable collamer lens surgery using in vivo confocal microscopy.
- Author
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Wei, Qiaoling, Chang, Weiteng, Jiang, Rui, Zhou, Xingtao, and Yu, Zhiqiang
- Subjects
ENDOTHELIAL cells ,CELL size ,STROMAL cells ,CONFOCAL microscopy ,ENDOTHELIUM - Abstract
Background: Implantable Collamer Lense (ICL) presents a viable alternative to conventional refractive surgeries, but their impact on corneal microstructure remains unclear. By employing in vivo confocal microscopy (IVCM), we examined changes in stromal and endothelial cells following the insertion of V4c ICLs, with the goal of enhancing post-surgical care and outcomes. Methods: In this longitudinal investigation, we conducted detailed preoperative assessments on 103 eyes from 53 participants. Follow-up evaluations were carried out after surgery at set intervals: one day, one week, one month, three months, six months, and twelve months. We used IVCM to analyze changes in stromal and endothelial cells. To assess differences between pre- and post-surgery variables and to investigate correlations with age, axial length (AL), and spherical equivalent refraction (SER), we applied a repeated measures mixed-effects model, with statistical significance set at P < 0.05. Results: No vision-threatening complications were reported post-surgery. Significant reductions in stromal cell density (SCD) were observed postoperatively, with anterior and mid- SCD reaching their lowest values at 3 months and posterior SCD at 1 month, remaining below baseline at 12 months. endothelial cell density (ECD) and percentage of hexagonal cells (PHC) decreased initially, recovering by 12 months. Conversely, endothelial cellular area (ECA) and coefficient of variation of cell size (CoV) increased postoperatively, with the most significant change at 1 week. Endothelial deposits were detected in 49 of 101 eyes on postoperative day 1, half of them were absorbed within 3 months post-surgery. Changes in posterior SCD were negatively related to AL, while AL, SER, lens thickness showed associated with endothelium changes. Conclusion: Our findings elucidate the corneal microstructural changes following V4c ICL implantation, particularly the significant early reductions in stromal and endothelial cell densities. We recommend careful management of viscoelastics during surgery to minimize endothelial deposits that may harm the endothelium. Enhanced early postoperative monitoring and these surgical adjustments can lead to improved surgical and post-surgical care, ultimately supporting better patient recovery. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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