86,827 results on '"Endothelium, Vascular"'
Search Results
2. Correlation of Markers of Inflammation and Endothelial Injury with Thrombosis in Left Atrium in Patients with Atria Fibrillation
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LI Jinyi, LIANG Guicheng, WANG Shirong, LI Shuhu, KE Honghong
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atrial fibrillation ,thromboembolism ,atrial function ,inflammatory factors ,endothelium, vascular ,Medicine - Abstract
Background Atrial fibrillation (AF) patients are prone to stroke and peripheral arterial embolism. Studying the pathogenesis of thrombosis formation in AF and providing effective interventions to reduce the risk is an important direction of clinical and basic research on AF. Objective To investigate the correlation of markers of inflammation and endothelial injury with thrombosis in the left atrium (LA) in AF patients. Methods Twenty-nine patients with valvular heart disease and 10 patients with coronary heart disease who underwent thoracotomy at the First Affiliated Hospital of Guangxi Medical University from July 2017 to December 2019 were selected, and divided into sinus rhythm group (15 cases) and AF group 〔24 cases, including 12 with left atrial appendage thrombus (LAAT), and 12 without LAAT〕 according to heart rhythm. General demographics were collected. Besides that, other data were also collected, including left atrial diameter (LAD) and left ventricular ejection fraction (LVEF), levels of protein kinase B (AKT), nuclear factor-κ B (NF-κ B), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF-α), endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (VWF), intercellular adhesion molecule (ICAM-1) and vascular cell adhesion factor (VCAM-1) in the left atrial blood sample, and calculated thrombus area in patients with AF and LAAT. The relationships of LAD, LVEF, markers of inflammation and endothelial injury with calculated area of thrombus in AF with LAAT patients were analyzed by Pearson correlation. Results There were significant differences in LAD and LVEF between sinus rhythm patients and AF patients with or without LAAT (P0.05). AF patients without LAAT had higher levels of AKT, NF-κB, IL-8, ET-1, ICAM-1 and VCAM-1 and lower NO level in left atrium than patients with sinus rhythm (P0.05). The maximum area, minimum area, and average area of the left atrial appendage thrombus in AF patients with LAAT were 4.8 cm2, 1.67 cm2, and (3.48±0.83) cm2, respectively. Pearson correlation analysis showed LAD, LVEF, AKT, NF-κB, hs-CRP, IL-6, IL-8, TNF-α, ET-1, NO, vWF, ICAM-1, and VCAM-1 had no linear correlation with the area of thrombus in AF patients with LAAT (P>0.05) . Conclusion Increased levels of markers of inflammation and endothelial injury in left atrium were found in AF patients, which were even more higher when the patients also had LAAT. Detecting the markers of inflammation and endothelial injury in left atrium is helpful to evaluate the thrombus prevalence in AF patients.
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- 2022
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3. Effects of photobiomodulation therapy (PBMT) over endothelial function in healthy individuals: a preliminary crossover clinical trial.
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Hauck, Melina, Schardong, Jociane, Donini, Gabriela, Normann, Tatiana Coser, and Plentz, Rodrigo Della Méa
- Abstract
Photobiomodulation therapy (PBMT) causes stimulatory effects that raise cell metabolism. The study aimed to evaluate the effects of PBMT on the endothelial function of healthy individuals. It was a controlled, randomized, crossover, triple-blind trial with 22 healthy volunteers (female: 77.3%), aged 25.45 years which were randomly divided into three groups. PBMT with gallium-aluminum-arsenide (GaAlAs) diode laser (810 nm, continuous-wave mode, 1000 mW, 0.28 cm2) was applied over the radial and ulnar artery regions in two parallel spots: group 1—30 J (n = 22, 107 J/cm2) per spot; group 2—60 J (n = 22, 214 J/cm2) per spot; and group 3—placebo (n = 22, sham). The endothelial function was measured before and immediately after PBMT by the flow-mediated dilation technique (%FMD) with high-resolution ultrasound. Statistical analysis was made with ANOVA for repeated measures, the effect size was measured by Cohen’s d, and results are presented as mean and standard error (or 95% confidence intervals). A p-value < 0.05 was considered statistically significant. The %FMD increases 10.4% with 60 J (mean difference = 0.496 mm, 95% CI = 0.42 to 0.57, p < 0.001), 7.3% with 30 J (mean difference = 0.518 mm, 95% CI = 0.44 to 0.59, p < 0.001), and 4.7% with placebo (mean difference = 0.560 mm, 95% CI = 0.48 to 0.63, p < 0.001). We found a small effect size (p = 0.702; d de Cohen = 0.24) without statistical difference between interventions. PBMT with the energy density of 60 J and 30 J did not improve endothelial function. Trial registration number: NCT03252184 (01/09/2017). [ABSTRACT FROM AUTHOR]
- Published
- 2023
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4. Mechanisms Regulating T Cell-Endothelial Cell Interactions
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Pilar Alcaide
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Inflammation ,T-Lymphocytes ,Cell Adhesion ,Leukocytes ,Endothelial Cells ,Humans ,Cell Communication ,Endothelium, Vascular ,General Biochemistry, Genetics and Molecular Biology - Abstract
T-cell interaction with the endothelial cells lining the vessel wall is a necessary step in the inflammatory response that allows T cells to extravasate from the circulation and migrate to sites of infectious or sterile inflammation. On one hand, the vascular endothelium is activated and, as a result, switches from an anti-adhesive to a pro-adhesive state, allowing adhesion of T cells and other leukocytes. On the other hand, T cells express ligands of endothelial adhesion molecules to sustain these interactions that eventually result in T-cell extravasation into sites of inflammation. A better understanding of the central players mediating these interactions may help develop novel therapeutics that modulate this process by preventing T-cell migration and inflammation. Here, I summarize current knowledge on the nature of these interactions in the context of inflammation and cancer immunotherapy.
- Published
- 2024
5. Plasma Cell-Free DNA Predicts Survival and Maps Specific Sources of Injury in Pulmonary Arterial Hypertension.
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Brusca, Samuel B., Elinoff, Jason M., Zou, Yvette, Jang, Moon Kyoo, Kong, Hyesik, Demirkale, Cumhur Y., Sun, Junfeng, Seifuddin, Fayaz, Pirooznia, Mehdi, Valantine, Hannah A., Tanba, Carl, Chaturvedi, Abhishek, Graninger, Grace M., Harper, Bonnie, Chen, Li-Yuan, Cole, Justine, Kanwar, Manreet, Benza, Raymond L., Preston, Ioana R., and Agbor-Enoh, Sean
- Abstract
Background: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown.Methods: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7-8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests.Results: In cohort A, median (interquartile range) age was 62 years (47-71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4-9). In cohort B, median (interquartile range) age was 59 years (49-71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6-9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P≤0.002) and were greater in the high-risk compared with the low-risk category (P≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P=0.0001) and REVEAL risk groups (log-rank: P<0.0001) each predicted transplant-free survival. The addition of cfDNA to REVEAL improved discrimination (area under the receiver operating characteristic curve, 0.72-0.78; P=0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P<0.05). cfDNA concentrations derived from erythrocyte progenitor cells, cardiac myocytes, and vascular endothelium were greater in patients with PAH with high-risk versus low-risk REVEAL scores (P≤0.02).Conclusions: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2022
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6. [Value of the biomarker soluble tyrosine kinase 1 type fms (sFLT-1) in the diagnosis and prognosis of sepsis: a systematic review].
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Ugalde MJ, Caballero A, Martín Fernández M, Tamayo E, and de la Varga-Martínez O
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- Humans, Prognosis, Shock, Septic diagnosis, Shock, Septic blood, Endothelium, Vascular, Vascular Endothelial Growth Factor Receptor-1 blood, Sepsis diagnosis, Sepsis blood, Biomarkers blood
- Abstract
Introduction: The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022., Materials and Methods: A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry)., Results: The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction., Conclusions: It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2024
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7. Vascular Health in Adults Born After Using Assisted Reproductive Technologies.
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Langer M, Vilsmaier T, Kramer M, Sciuk F, Kolbinger B, Li P, Jakob A, Rogenhofer N, Dalla-Pozza R, Thaler C, Haas NA, and Oberhoffer FS
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- Humans, Female, Male, Pilot Projects, Young Adult, Adult, Blood Pressure, Endothelium, Vascular, Fertilization in Vitro, Cardiovascular Diseases etiology, Sperm Injections, Intracytoplasmic, Lipids blood, Reproductive Techniques, Assisted, Carotid Intima-Media Thickness, Pulse Wave Analysis
- Abstract
An increasing number of children are conceived by assisted reproductive technologies (ART). Several studies indicated vascular alterations in ART children. However, limited data is available within the adult ART population. Therefore, this study investigated the overall vascular health of young ART adults in comparison to spontaneously conceived peers. In total, 16 ART subjects and 22 spontaneously conceived peers (22.06 ± 2.21 years vs. 22.00 ± 2.14 years, p = 0.194) were enrolled for the assessment of endothelial function, brachial blood pressure, central blood pressure, pulse wave velocity, carotid intima-media thickness, and blood lipids. No significant differences in vascular function were detected between the in vitro fertilization subgroup (n = 9), the intracytoplasmic sperm injection subgroup (n = 7) and spontaneously conceived peers. This pilot study suggests an unimpaired vascular function in young ART adults. In the future, multi-centric studies with a greater sample size are required to confirm the results of the current study and enable precise cardiovascular risk stratification of the adult ART population., (© 2022. The Author(s).)
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- 2024
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8. Association between estimated glomerular filtration rate (eGFR) and asymmetric dimethylarginine (ADMA) concentrations among the elderly in a rural community: a cross-sectional study
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Hye Rin Choi, Seung Won Lee, Da-Hye Jeon, Nam Wook Hur, Yoosik Youm, and Hyeon Chang Kim
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Glomerular filtration rate ,Endothelium, vascular ,Aged ,Rural population ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background Reduced glomerular filtration rate and increased asymmetric dimethylarginine (ADMA) are prevalent in elderly people. However, most of the studies that have examined the association between the two conditions were performed in patients with renal dysfunction, but not in the general elderly population. Thus, we investigated an association between estimated glomerular filtration rate (eGFR) and ADMA concentration among community-dwelling older Koreans. Methods A cross-sectional study was conducted on 269 men and 382 women (mean age, 71.6 years) enrolled in the Korean Social Life, Health, and Aging Project (KSHAP), a population-based cohort study of health determinants in elderly Koreans. We calculated eGFR using chronic kidney disease- Epidemiology Collaboration Group (CKD-EPI) equation. ADMA concentration was measured by an enzyme-linked immunosorbent assay. The association between eGFR and ADMA concentrations was analyzed by multiple linear regression models. Results The mean ADMA was significantly higher in people with eGFR
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- 2019
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9. Vascular dysfunction in hemorrhagic viral fevers: opportunities for organotypic modeling.
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Zarate-Sanchez E, George SC, Moya ML, and Robertson C
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- Humans, Animals, Endothelial Cells pathology, Endothelium, Vascular, Models, Biological, Hemorrhagic Fevers, Viral virology
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The hemorrhagic fever viruses (HFVs) cause severe or fatal infections in humans. Named after their common symptom hemorrhage, these viruses induce significant vascular dysfunction by affecting endothelial cells, altering immunity, and disrupting the clotting system. Despite advances in treatments, such as cytokine blocking therapies, disease modifying treatment for this class of pathogen remains elusive. Improved understanding of the pathogenesis of these infections could provide new avenues to treatment. While animal models and traditional 2D cell cultures have contributed insight into the mechanisms by which these pathogens affect the vasculature, these models fall short in replicating in vivo human vascular dynamics. The emergence of microphysiological systems (MPSs) offers promising avenues for modeling these complex interactions. These MPS or 'organ-on-chip' models present opportunities to better mimic human vascular responses and thus aid in treatment development. In this review, we explore the impact of HFV on the vasculature by causing endothelial dysfunction, blood clotting irregularities, and immune dysregulation. We highlight how existing MPS have elucidated features of HFV pathogenesis as well as discuss existing knowledge gaps and the challenges in modeling these interactions using MPS. Understanding the intricate mechanisms of vascular dysfunction caused by HFV is crucial in developing therapies not only for these infections, but also for other vasculotropic conditions like sepsis., (Creative Commons Attribution license.)
- Published
- 2024
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10. Intermediate versus morning chronotype has lower vascular insulin sensitivity in adults with obesity.
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Malin SK, Remchak ME, Heiston EM, Battillo DJ, Gow AJ, Shah AM, and Liu Z
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- Adult, Humans, Female, Chronotype, Nitrates, Obesity, Brachial Artery physiology, Insulin, Endothelium, Vascular, Vasodilation, Arginine, Insulin Resistance, Cardiovascular Diseases
- Abstract
Aim: Chronotype reflects a circadian rhythmicity that regulates endothelial function. While the morning chronotype (MORN) usually has low cardiovascular disease risk, no study has examined insulin action on endothelial function between chronotypes. We hypothesized intermediate chronotypes (INT) would have lower vascular insulin sensitivity than morning chronotype (MORN)., Materials and Methods: Adults with obesity were classified per Morningness-Eveningness Questionnaire (MEQ) as either MORN (n = 27, 22 female, MEQ = 63.7 ± 4.7, 53.8 ± 6.7 years, 35.3 ± 4.9 kg/m
2 ) or INT (n = 29, 23 female, MEQ = 48.8 ± 6.7, 56.6 ± 9.0 years, 35.7 ± 6.1 kg/m2 ). A 120 min euglycaemic-hyperinsulinaemic clamp (40 mU/m2 /min, 90 mg/dl) was conducted to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD; conduit artery), post-ischaemic flow velocity (resistance arteriole), as well as microvascular insulin sensitivity via contrast-enhanced ultrasound [e.g. microvascular blood volume (perfusion)]. Fasting plasma arginine and citrulline, as well as fasting and clamp-derived plasma endothelin-1 and nitrate/nitrite, were assessed as surrogates of vasoconstriction and nitric oxide-mediated vasodilation. Aerobic fitness (VO2 max) and body composition (dual-energy X-ray absorptiometry) were also collected., Results: MORN had a higher VO2 max compared with INT (p < .01), although there was no difference in fat mass. While fasting FMD was similar between groups, insulin lowered FMD corrected to shear stress and microvascular blood volume in INT compared with MORN after co-varying for VO2 max (both p ≤ .02). INT also had a lower fasting nitrate (p = .03) and arginine (p = .07). Higher MEQ correlated with elevated FMD (r = 0.33, p = .03) and lower post-ischaemic flow velocity (r = -0.33, p = .03) as well as shear rate (r = -0.36, p = .02) at 120 min., Conclusion: When measured during the morning, INT had a lower vascular insulin sensitivity than MORN. Additional work is needed to understand endothelial function differences among chronotypes to optimize cardiovascular disease risk reduction., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)- Published
- 2024
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11. A high-resolution view of the heterogeneous aging endothelium.
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Dobner S, Tóth F, and de Rooij LPMH
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- Endothelial Cells physiology, Cellular Senescence, Endothelium, Vascular
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Vascular endothelial cell (EC) aging has a strong impact on tissue perfusion and overall cardiovascular health. While studies confined to the investigation of aging-associated vascular readouts in one or a few tissues have already drastically expanded our understanding of EC aging, single-cell omics and other high-resolution profiling technologies have started to illuminate the intricate molecular changes underlying endothelial aging across diverse tissues and vascular beds at scale. In this review, we provide an overview of recent insights into the heterogeneous adaptations of the aging vascular endothelium. We address critical questions regarding tissue-specific and universal responses of the endothelium to the aging process, EC turnover dynamics throughout lifespan, and the differential susceptibility of ECs to acquiring aging-associated traits. In doing so, we underscore the transformative potential of single-cell approaches in advancing our comprehension of endothelial aging, essential to foster the development of future innovative therapeutic strategies for aging-associated vascular conditions., (© 2024. The Author(s).)
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- 2024
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12. Evidence of premature vascular dysfunction in young adults who regularly use e-cigarettes and the impact of usage length.
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Matheson C, Simovic T, Heefner A, Colon M, Tunon E, Cobb K, Thode C, Breland A, Cobb CO, Nana-Sinkam P, Garten R, and Rodriguez-Miguelez P
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- Humans, Young Adult, Vasodilation physiology, Endothelium, Vascular, Electronic Nicotine Delivery Systems
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Background: Electronic (e-) cigarettes are increasingly popular tobacco products on the US market. Traditional tobacco products are known to cause vascular dysfunction, one of the earliest indicators of cardiovascular disease (CVD) development. However, little is known about the effect of regular e-cigarette use on vascular function. The purpose of this study was to investigate the impact of regular e-cigarette use on vascular function and cardiovascular health in young, healthy adults., Methods: Twenty-one regular users of e-cigarettes (ECU) and twenty-one demographically matched non-users (NU) completed this study. Vascular health was assessed in the cutaneous microcirculation through different reactivity tests to evaluate overall functionality, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID). Macrovascular function was assessed using flow-mediated dilation (FMD)., Results: Our results suggest that regular users of e-cigarettes present with premature microvascular impairment when compared to non-users. Specifically, they exhibit lower hyperemic (p = 0.003), thermal (p = 0.010), and EDD (p = 0.004) responses. No differences in EID between the groups were identified. We also identified that individuals who use e-cigarettes for longer than 3 years also present with systemic manifestations, as observed by significantly reduced macrovascular (p = 0.002) and microvascular (p ≤ 0.044) function., Conclusions: Our novel data suggests that young, apparently healthy, regular users of e-cigarettes present with premature vascular dysfunction in the microcirculation when compared to non-users. We have also identified systemic vascular dysfunction affecting both the micro and macrovasculature in those young individuals who used e-cigarettes for longer than 3 years. Taken together, these findings associate regular e-cigarette use with premature vascular dysfunctions and adverse cardiovascular outcomes., (© 2024. The Author(s).)
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- 2024
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13. Remnant cholesterol trajectory and subclinical arteriosclerosis: a 10-year longitudinal study of Chinese adults.
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Yang PT, Tang L, Yang SQ, Shi QL, Wang YQ, Qin YX, Wang JG, and Li Y
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- Adult, Humans, Longitudinal Studies, Ankle Brachial Index, Endothelium, Vascular, Pulse Wave Analysis, Cholesterol, China epidemiology, Risk Factors, Atherosclerosis epidemiology, Vascular Stiffness
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We aimed to identify different trajectories of remnant cholesterol (RC) and investigate the association of RC trajectories with vascular endothelial function and atherosclerosis progression in a longitudinal cohort of the Chinese population. A total of 521 participants were included in the flow-mediated vasodilation (FMD) subcohort study, and 7775 participants were included in the brachial-ankle pulse wave velocity (baPWV) subcohort study. All participants had ≥ 3 medical examinations during the 10-year follow-up period. In the FMD subcohort study, three distinct RC trajectories were identified according to the RC range and changing pattern over time: "low" (57.58%), "moderate" (30.90%) and "high" (11.52%). The proportion of the three groups with vascular endothelial dysfunction (FMD < 7.0%) was 20.00%, 39.75% and 60.00% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.88 and 2.94 times the odds of vascular endothelial dysfunction (P = 0.048). In the baPWV subcohort study, three distinct RC trajectories were also identified: "low" (54.29%), "moderate" (38.97%) and "high" (6.74%). The proportion of the three groups with atherosclerosis (baPWV > 1400 cm/s) was 38.79%, 51.26% and 59.01% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.46 and 2.16 times the odds of atherosclerosis (P < 0.001). The findings indicated that distinct RC trajectories are significantly associated with vascular endothelial function and atherosclerosis. Regular monitoring to identify persistent increases in RC may be more helpful in identifying individuals with a high risk of cardiovascular disease., (© 2024. The Author(s).)
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- 2024
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14. Vasorelaxant effects of ellagitannins isolated from Cuphea carthagenensis.
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Isla KKY, Tanae MM, de Lima-Landman MTR, de Magalhães PM, Lapa AJ, and Souccar C
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- Rats, Animals, Vasodilator Agents pharmacology, Hydrolyzable Tannins pharmacology, Rats, Wistar, Endothelial Cells, Vasodilation, Endothelium, Vascular, Nitric Oxide metabolism, Aorta, Thoracic metabolism, NG-Nitroarginine Methyl Ester pharmacology, Cuphea metabolism, Hypotension
- Abstract
Cuphea carthagenensis (Jacq.) J. F. Macbr. is a popular plant in Brazilian folk medicine owing to its hypotensive and central nervous system depressant effects. This study aimed to validate the hypotensive effect of the plant's aqueous extract (AE) in rats and examine the vascular actions of three hydrolyzable tannins, oenothein B, woodfordin C, and eucalbanin B, isolated from AE. Systolic blood pressure in unanesthetized rats was determined using the non-invasive tail-cuff method. Oral treatment of normotensive rats with 0.5 and 1.0 g/kg/day AE induced a dose-related hypotensive effect after 1 week. In rat aortic rings pre-contracted with noradrenaline, all ellagitannins (20 - 180 µM) induced a concentration-related vasorelaxation. This effect was blocked by either removing the endothelium or pre-incubating with N
G -nitro-l-arginine methyl ester (10 µM), an inhibitor of nitric oxide (NO) synthase. In KCl-depolarized rat portal vein preparations, the investigated compounds did not affect significantly the maximal contractile responses and pD2 values of the concentration-response curves to CaCl2 . Our results demonstrated the hypotensive effect of C. carthagenensis AE in unanesthetized rats. All isolated ellagitannins induced vasorelaxation in vitro via activating NO synthesis/NO release from endothelial cells, without altering the Ca2+ influx in vascular smooth muscle preparations. Considering the low oral bioavailability of ellagitannins, the determined in vitro actions of these compounds are unlikely to account for the hypotensive effect of AE in vivo . It remains to be determined the role of the bioactive ellagitannin-derived metabolites in the hypotensive effect observed after oral treatment of unanesthetized rats with the plant extract., Competing Interests: The authors declare that they have no conflicts of interest., (Thieme. All rights reserved.)- Published
- 2024
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15. Evaluation of endothelial dysfunction in hypertensive children and adolescents.
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Doğan K, Başar EZ, Aytaç MB, Şahin N, Bayrak YE, Bek K, Güngör HS, Sönmez HE, and Babaoğlu K
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- Male, Female, Child, Humans, Adolescent, Carotid Intima-Media Thickness, Cross-Sectional Studies, Essential Hypertension, Endothelium, Vascular, Vasodilation, Hypertension, Atherosclerosis complications
- Abstract
Background: Atherosclerotic changes can be attributed to early endothelial damage in individuals with hypertension. We aimed to explore the relationship between endothelial dysfunction and hypertension in newly diagnosed children without end-organ damage, considering carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), and functional capillaroscopy parameters. We also analyzed the differences between dipper and non-dipper patients., Methods: In this cross-sectional study, 20 patients diagnosed with essential hypertension with no target organ damage, and 20 age and sex-matched healthy volunteers were enrolled. The patient group comprised newly diagnosed individuals not receiving antihypertensive treatment. Hypertensive patients were divided into two groups (dipper and non-dipper patients). The measurements of CIMT, brachial FMD, and functional capillaroscopy were performed before starting treatment., Results: Among the patients, 11 were boys, and 9 were girls, with a median age of 16.0 (2.13) years. Of 20 hypertensive patients, 10 were dipper and 10 were non-dipper. Significant differences were observed between the hypertensive patients and controls in terms of CIMT (p = 0.04), brachial artery FMD (p = 0.02), and functional capillary density (p < 0.001). Hypertensive patients exhibited increased CIMT, reduced brachial artery FMD, and lower capillary density. However, there were no differences between dippers and non-dippers regarding age, sex, height SDS, weight SDS, CIMT SDS, brachial artery FMD, and capillary density., Conclusions: Understanding the vascular consequences associated with essential hypertension emphasizes the importance of early detection and management of hypertension. Herein, we have effectively highlighted significant endothelial changes through the analysis of three parameters in newly diagnosed children without apparent target organ damage., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)
- Published
- 2024
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16. Fundamental considerations for designing endothelialized in vitro models of thrombosis.
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Lemmens TP, Bröker V, Rijpkema M, Hughes CCW, Schurgers LJ, and Cosemans JMEM
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- Humans, Endothelium, Vascular, Endothelial Cells metabolism, Thrombosis metabolism
- Abstract
Endothelialized in vitro models for cardiovascular disease have contributed greatly to our current understanding of the complex molecular mechanisms underlying thrombosis. To further elucidate these mechanisms, it is important to consider which fundamental aspects to incorporate into an in vitro model. In this review, we will focus on the design of in vitro endothelialized models of thrombosis. Expanding our understanding of the relation and interplay between the different pathways involved will rely in part on complex models that incorporate endothelial cells, blood, the extracellular matrix, and flow. Importantly, the use of tissue-specific endothelial cells will help in understanding the heterogeneity in thrombotic responses between different vascular beds. The dynamic and complex responses of endothelial cells to different shear rates underlines the importance of incorporating appropriate shear in in vitro models. Alterations in vascular extracellular matrix composition, availability of bioactive molecules, and gradients in concentration and composition of these molecules can all regulate the function of both endothelial cells and perivascular cells. Factors modulating these elements in in vitro models should therefore be considered carefully depending on the research question at hand. As the complexity of in vitro models increases, so can the variability. A bottom-up approach to designing such models will remain an important tool for researchers studying thrombosis. As new techniques are continuously being developed and new pathways are brought to light, research question-dependent considerations will have to be made regarding what aspects of thrombosis to include in in vitro models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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17. Vascular protein disulfide isomerase A1 mediates endothelial dysfunction induced by angiotensin II in mice.
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Kij A, Bar A, Czyzynska-Cichon I, Przyborowski K, Proniewski B, Mateuszuk L, Kurylowicz Z, Jasztal A, Buczek E, Kurpinska A, Suraj-Prazmowska J, Marczyk B, Matyjaszczyk-Gwarda K, Daiber A, Oelze M, Walczak M, and Chlopicki S
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- Mice, Male, Animals, Protein Disulfide-Isomerases metabolism, Protein Disulfide-Isomerases pharmacology, Pulse Wave Analysis, Thrombin metabolism, Thrombin pharmacology, Mice, Inbred C57BL, Nitric Oxide Synthase Type III metabolism, Endothelium, Vascular, Nitric Oxide metabolism, Angiotensin II pharmacology, Angiotensin II metabolism, Vascular Diseases metabolism
- Abstract
Aim: Protein disulfide isomerases (PDIs) are involved in platelet aggregation and intravascular thrombosis, but their role in regulating endothelial function is unclear. Here, we characterized the involvement of vascular PDIA1 in angiotensin II (Ang II)-induced endothelial dysfunction in mice., Methods: Endothelial dysfunction was induced in C57BL/6JCmd male mice via Ang II subcutaneous infusion, and PDIA1 was inhibited with bepristat. Endothelial function was assessed in vivo with magnetic resonance imaging and ex vivo with a myography, while arterial stiffness was measured as pulse wave velocity. Nitric oxide (NO) bioavailability was measured in the aorta (spin-trapping electron paramagnetic resonance) and plasma (NO
2 - and NO3 - levels). Oxidative stress, eNOS uncoupling (DHE-based aorta staining), and thrombin activity (thrombin-antithrombin complex; calibrated automated thrombography) were evaluated., Results: The inhibition of PDIA1 by bepristat in Ang II-treated mice prevented the impairment of NO-dependent vasodilation in the aorta as evidenced by the response to acetylcholine in vivo, increased systemic NO bioavailability and the aortic NO production, and decreased vascular stiffness. Bepristat's effect on NO-dependent function was recapitulated ex vivo in Ang II-induced endothelial dysfunction in isolated aorta. Furthermore, bepristat diminished the Ang II-induced eNOS uncoupling and overproduction of ROS without affecting thrombin activity., Conclusion: In Ang II-treated mice, the inhibition of PDIA1 normalized the NO-ROS balance, prevented endothelial eNOS uncoupling, and, thereby, improved vascular function. These results indicate the importance of vascular PDIA1 in regulating endothelial function, but further studies are needed to elucidate the details of the mechanisms involved., (© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)- Published
- 2024
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18. Exercise training and vascular heterogeneity in db/db mice: evidence for regional- and duration-dependent effects.
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Sallam NA, Wang B, and Laher I
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- Mice, Animals, Proto-Oncogene Proteins c-akt metabolism, Vasodilation, Mice, Inbred Strains, Nitric Oxide Synthase Type III metabolism, Endothelium, Vascular, Inflammation metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Experimental metabolism
- Abstract
Exercise training (ET) has several health benefits; however, our understanding of regional adaptations to ET is limited. We examined the functional and molecular adaptations to short- and long-term ET in elastic and muscular conduit arteries of db/db mice in relation to changes in cardiovascular risk factors. Diabetic mice and their controls were exercised at moderate intensity for 4 or 8 weeks. The vasodilatory and contractile responses of thoracic aortae and femoral arteries isolated from the same animals were examined. Blood and aortic samples were used to measure hyperglycemia, oxidative stress, inflammation, dyslipidemia, protein expression of SOD isoforms, COX, eNOS, and Akt. Short-term ET improved nitric oxide (NO) mediated vasorelaxation in the aortae and femoral arteries of db/db mice in parallel with increased SOD2 and SOD3 expression, reduced oxidative stress and triglycerides, and independent of weight loss, glycemia, or inflammation. Long-term ET reduced body weight in parallel with reduced systemic inflammation and improved insulin sensitivity along with increased SOD1, Akt, and eNOS expression and improved NO vasorelaxation. Exercise did not restore NOS- and COX-independent vasodilatation in femoral arteries, nor did it mitigate the hypercontractility in the aortae of db/db mice; rather ET transiently increased contractility in association with upregulated COX-2. Long-term ET differentially affected the aortae and femoral arteries contractile responses. ET improved NO-mediated vasodilation in both arteries likely due to collective systemic effects. ET did not mitigate all diabetes-induced vasculopathies. Optimization of the ET regimen can help develop comprehensive management of type 2 diabetes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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19. Seasonal variations in endothelium-dependent flow-mediated vasodilation and endothelium-independent nitroglycerine-induced vasodilation.
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Maruhashi T, Kajikawa M, Kishimoto S, Yamaji T, Harada T, Hashimoto Y, Mizobuchi A, Tanigawa S, Yusoff FM, Nakano Y, Chayama K, Nakashima A, Goto C, and Higashi Y
- Subjects
- Humans, Seasons, Nitroglycerin pharmacology, Brachial Artery, Vasodilation, Endothelium, Vascular
- Abstract
Cardiovascular mortality has been shown to vary seasonally. However, it has not been determined whether vascular function is affected by the season. The purpose of this study was to investigate the associations of vascular function with season and outdoor temperature. Between April 2007 and March 2022, measurements of flow-mediated vasodilation (FMD) of the brachial artery as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of endothelium-independent vasodilation were performed in 2190 subjects. There was no significant seasonal difference in FMD (spring, 3.9 ± 3.1%; summer, 3.5 ± 3.0%; fall, 3.7 ± 3.0%; winter, 3.6 ± 3.2%; P = 0.14). There was no significant correlation between FMD and daily mean outdoor temperature (r = -0.02, P = 0.25). Multivariate analyses revealed that neither season (β = -0.020, P = 0.31) nor outdoor temperature (β = 0.005, P = 0.81) was significantly associated with FMD after adjustment for other confounding factors. There were significant seasonal differences in NID (spring, 12.8 ± 6.3%; summer, 12.0 ± 6.1%; fall, 11.7 ± 6.1%; winter, 12.3 ± 5.9%; P = 0.02). However, multivariate analysis revealed that there was no significant association between season and NID after adjustment for other confounding factors (β = -0.012, P = 0.56). There was no significant correlation between NID and daily outdoor mean temperature (r = -0.03, P = 0.17). Multivariate analysis revealed that outdoor temperature was not significantly associated with NID (β = -0.006, P = 0.78). There was no significant association of FMD or NID with season or outdoor temperature, suggesting that it is not necessary to take into account the effects of season and outdoor temperature on vascular function when interpreting the results of FMD and NID measurements. Public trials registry number: UMIN000039512., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)
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- 2024
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20. The interaction between particles and vascular endothelium in blood flow.
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Li X, Zou J, He Z, Sun Y, Song X, and He W
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- Humans, Drug Delivery Systems, Particle Size, Endothelium, Vascular, Hemodynamics
- Abstract
Particle-based drug delivery systems have shown promising application potential to treat human diseases; however, an incomplete understanding of their interactions with vascular endothelium in blood flow prevents their inclusion into mainstream clinical applications. The flow performance of nano/micro-sized particles in the blood are disturbed by many external/internal factors, including blood constituents, particle properties, and endothelium bioactivities, affecting the fate of particles in vivo and therapeutic effects for diseases. This review highlights how the blood constituents, hemodynamic environment and particle properties influence the interactions and particle activities in vivo. Moreover, we briefly summarized the structure and functions of endothelium and simulated devices for studying particle performance under blood flow conditions. Finally, based on particle-endothelium interactions, we propose future opportunities for novel therapeutic strategies and provide solutions to challenges in particle delivery systems for accelerating their clinical translation. This review helps provoke an increasing in-depth understanding of particle-endothelium interactions and inspires more strategies that may benefit the development of particle medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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21. PCSK9抑制剂在ox-LDL诱导HUVECs损伤中的 保护作用研究.
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许景涵, 左俊荣, 韩楚仪, 李婷婷, 金冬霞, 赵福梅, and 丛洪良
- Abstract
Objective To investigate the protective mechanism of PCSK9 inhibitor against oxidative low-density lipoprotein (ox-LDL) induced injury of human umbilical vein endothelial cells (HUVECs). Methods HUVECs in logarithmic growth phase were divided into Control group (normal culture group), ox-LDL group (induced by 50 mg/L oxLDL for 24 h) and PCSK9 inhibitor groups (low, medium and high dose of PCSK9 inhibitor). The low, medium and high dose of PCSK9 inhibitor groups were treated with 5, 10 and 20 µmol/L PCSK9 inhibitors for 24 h and then induced by 50 mg/L ox-LDL for 24 h. Cell activity was detected by CCK-8 assay, and cell survival rates were calculated. Transcription and secretion levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in supernatant of cell culture were determined by quantitative real time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins (Bax, Bcl-2, Cleaved-Caspase-3) and nuclear factor-κB (NF-κB) signaling pathway related proteins were detected by Western blot assay. Results Compared with the Control group, the cell survival rate was decreased, transcriptional and secretion levels of TNF-α, IL-6, MCP-1 were increased, apoptosis rate increased, pro-apoptotic proteins (Bax and cleaved Caspase-3) up-regulated, anti-apoptotic protein Bcl-2 down- regulated and phosphorylated NF-κB (p-NF-κB) expression increased in ox-LDL group. Meanwhile, the expression of NF-κB was up-regulated in the nucleus and down regulated in cytoplasm. Compared with ox-LDL group, the survival rates were increased in medium and high dose PCSK9 inhibitor groups after treatment with PCSK9 inhibitor. The transcription and secretion levels of TNF-α, IL-6, MCP-1 and apoptosis rate decreased. The results of Western blot assay showed that the expression levels of Bax and cleaved-Caspase-3 downregulated, Bcl-2 up-regulated and p-NF-κB decreased. PCSK9 inhibitors down-regulated the expression of NF-κB in the nucleus and up-regulated the expression of NF-κB in cytoplasm of HUVECs induced by ox-LDL (P < 0.05). Conclusion PCSK9 inhibitors can inhibit ox-LDL induced inflammatory response and cell apoptosis in HUVECs and play a protective role. [ABSTRACT FROM AUTHOR]
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- 2021
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22. SOLUBLE GUANYLYL CYCLASE ACTIVATION RESCUES HYPEROXIA-INDUCED DYSFUNCTION OF VASCULAR RELAXATION
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Eric H. Mace, Melissa J. Kimlinger, Tom J. No, Sergey I. Dikalov, Cassandra Hennessy, Matthew S. Shotwell, Frederic T. Billings, and Marcos G. Lopez
- Subjects
Nitroprusside ,Vasodilator Agents ,Heme ,Hyperoxia ,Critical Care and Intensive Care Medicine ,Nitric Oxide ,Acetylcholine ,Vasodilation ,Oxygen ,Mice ,Soluble Guanylyl Cyclase ,Superoxides ,Emergency Medicine ,Animals ,Endothelium, Vascular - Abstract
Introduction: Perioperative alterations in perfusion lead to ischemia and reperfusion injury, and supplemental oxygen is administered during surgery to limit hypoxic injury but can lead to hyperoxia. We hypothesized that hyperoxia impairs endothelium-dependent and endothelium-independent vasodilation but not the vasodilatory response to heme-independent soluble guanylyl cyclase activation. Methods: We measured the effect of oxygen on vascular reactivity in mouse aortas. Mice were ventilated with 21% (normoxia), 60% (moderate hyperoxia), or 100% (severe hyperoxia) oxygen during 30 minutes of renal ischemia and 30 minutes of reperfusion. After sacrifice, the thoracic aorta was isolated, and segments mounted on a wire myograph. We measured endothelium-dependent and endothelium-independent vasodilation with escalating concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, and we measured the response to heme-independent soluble guanylyl cyclase activation with cinaciguat. Vasodilator responses to each agonist were quantified as the maximal theoretical response ( Emax ) and the effective concentration to elicit 50% relaxation (EC 50 ) using a sigmoid model and nonlinear mixed-effects regression. Aortic superoxide was measured with dihydroethidium probe and high-performance liquid chromatography quantification of the specific superoxide product 2-hydroxyethidium. Results: Hyperoxia impaired endothelium-dependent (ACh) and endothelium-independent (SNP) vasodilation compared with normoxia and had no effect on cinaciguat-induced vasodilation. The median ACh Emax was 76.4% (95% confidence interval = 69.6 to 83.3) in the normoxia group, 53.5% (46.7 to 60.3) in the moderate hyperoxia group, and 53.1% (46.3 to 60.0) in the severe hyperoxia group ( Plt; 0.001, effect across groups), while the ACh EC 50 was not different among groups. The SNP Emax was 133.1% (122.9 to 143.3) in normoxia, 128.3% (118.1 to 138.6) in moderate hyperoxia, and 114.8% (104.6 to 125.0) in severe hyperoxia ( Plt; 0.001, effect across groups), and the SNP EC 50 was 0.38 log M greater in moderate hyperoxia than in normoxia (95% confidence interval = 0.18 to 0.58, Plt; 0.001). Cinaciguat Emax and EC 50 were not different among oxygen treatment groups (median range Emax = 78.0% to 79.4% and EC 50 = -18.0 to -18.2 log M across oxygen groups). Aorta 2-hydroxyethidium was 1419 pmol/mg of protein (25th-75th percentile = 1178-1513) in normoxia, 1993 (1831-2473) in moderate hyperoxia, and 2078 (1936-2922) in severe hyperoxia ( P = 0.008, effect across groups). Conclusions: Hyperoxia, compared with normoxia, impaired endothelium-dependent and endothelium-independent vasodilation but not the response to heme-independent soluble guanylyl cyclase activation, and hyperoxia increased vascular superoxide production. Results from this study could have important implications for patients receiving high concentrations of oxygen and at risk for ischemia reperfusion-mediated organ injury.
- Published
- 2023
23. NOX2 and NOX5 are increased in cardiac microvascular endothelium of deceased COVID-19 patients
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Jiang, Zhu, Wu, Linghe, van der Leeden, Britt, van Rossum, Albert C, Niessen, Hans W M, Krijnen, Paul A J, Pathology, ACS - Heart failure & arrhythmias, ACS - Atherosclerosis & ischemic syndromes, Molecular cell biology and Immunology, Cardiology, and AII - Inflammatory diseases
- Subjects
NADPH Oxidase 5 ,Humans ,NADPH Oxidases ,COVID-19 ,Heart ,Endothelium, Vascular ,Reactive Oxygen Species ,Cardiology and Cardiovascular Medicine - Abstract
BACKGROUND: Cardiac injury and inflammation are common findings in COVID-19 patients. Autopsy studies have revealed cardiac microvascular endothelial damage and thrombosis in COVID-19 patients, indicative of microvascular dysfunction in which reactive oxygen species (ROS) may play a role. We explored whether the ROS producing proteins NOX2, NOX4 and NOX5 are involved in COVID-19-induced cardio-microvascular endothelial dysfunction.METHODS: Heart tissue were taken from the left (LV) and right (RV) ventricle of COVID-19 patients (n = 15) and the LV of controls (n = 14) at autopsy. The NOX2-, NOX4-, NOX5- and Nitrotyrosine (NT)-positive intramyocardial blood vessels fractions were quantitatively analyzed using immunohistochemistry.RESULTS: The LV NOX2+, NOX5+ and NT+ blood vessels fractions in COVID-19 patients were significantly higher than in controls. The fraction of NOX4+ blood vessels in COVID-19 patients was comparable with controls. In COVID-19 patients, the fractions of NOX2+, NOX5+ and NT+ vessels did not differ significantly between the LV and RV, and correlated positively between LV and RV in case of NOX5 (r = 0.710; p = 0.006). A negative correlation between NOX5 and NOX2 (r = -0.591; p = 0.029) and between NOX5 and disease time (r = -0.576; p = 0.034) was noted in the LV of COVID-19 patients.CONCLUSION: We show the induction of NOX2 and NOX5 in the cardiac microvascular endothelium in COVID-19 patients, which may contribute to the previously observed cardio-microvascular dysfunction in COVID-19 patients. The exact roles of these NOXes in pathogenesis of COVID-19 however remain to be elucidated.
- Published
- 2023
24. Device-guided slow breathing alters postprandial oxidative stress in young adult males: A randomized sham-controlled crossover trial
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Stacy D. Hunter, Luciano Bernardi, Matthew J. McAllister, Dinesh John, Mitra Rahimi, and Micqauella R. Lopez
- Subjects
Male ,Adult ,Blood Glucose ,Cross-Over Studies ,Nutrition and Dietetics ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Postprandial Period ,Thiobarbituric Acid Reactive Substances ,Diet ,Young Adult ,Oxidative Stress ,Humans ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine - Abstract
Slow, deep breathing (SDB) lowers blood pressure (BP) though the underlying mechanisms are unknown. Redox improvements could facilitate hemodynamic adjustments with SDB though this has not been investigated. The purpose of this randomized, sham-controlled trial was to examine the acute effects of SDB on oxidative stress and endothelial function during a physiological perturbation (high-fat meal) known to induce oxidative stress.Seventeen males (ages 18-35 years) were enrolled, and anthropometric measurements and 7-day physical activity monitoring were completed. Testing sessions consisted of 24-h diet recalls (ASA24), blood sample collection for superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) analysis, and flow-mediated dilation (FMD). High-fat meals were ingested and 2-min breathing exercises (SDB or sham control breathing) were completed every 15 min during the 4-h postprandial phase. Blood sample collection and FMD were repeated 1-, 2-, and 4-h post meal consumption. Mean body mass index and step counts were 25.6 ± 4.3 kg/mFindings from the current investigation suggest that SDB alters postprandial redox in the absence of changes in endothelial function in young, healthy males.NCT04864184.NCT04864184.
- Published
- 2023
25. [Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats].
- Author
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Lu G, Sun H, Sun Z, Liu L, Wang L, Zhang N, Wang Y, He Y, Ji J, Li X, Kang P, and Tang B
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- Rats, Animals, Blood Pressure, Endothelial Cells, Calcium, Calcium Chloride pharmacology, Nitroarginine pharmacology, Rats, Sprague-Dawley, 4-Aminopyridine pharmacology, Indomethacin pharmacology, Esters pharmacology, Endothelium, Vascular, Dose-Response Relationship, Drug, Aorta, Thoracic, Vasodilation, Chlorides, Triterpenes, Barium Compounds
- Abstract
Objective: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism., Methods: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl
2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release., Results: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2 -induced vascular contraction., Conclusion: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.- Published
- 2024
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26. Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.
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Rengarajan A, Goldblatt HE, Beebe DJ, Virumbrales-Muñoz M, and Boeldt DS
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- Pregnancy, Female, Humans, Cells, Cultured, Microphysiological Systems, Endothelium, Vascular, Human Umbilical Vein Endothelial Cells, Leukocytes, Mononuclear, Inflammation Mediators pharmacology
- Abstract
Functional assessment of endothelium serves as an important indicator of vascular health and is compromised in vascular disorders including hypertension, atherosclerosis, and preeclampsia. Endothelial dysfunction in these cases is linked to dysregulation of the immune system involving both changes to immune cells and increased secretion of inflammatory cytokines. Herein, we utilize a well-established microfluidic device to generate a 3-dimensional vascular microphysiological system (MPS) consisting of a tubular blood vessel lined with human umbilical vein endothelial cells (HUVECs) to evaluate endothelial function measured via endothelial permeability and Ca
2+ signaling. We evaluated the effect of a mixture of factors associated with inflammation and cardiovascular disease (TNFα, VEGF-A, IL-6 at 10 ng ml-1 each) on vascular MPS and inferred that inflammatory mediators contribute to endothelial dysfunction by disrupting the endothelial barrier over a 48 hour treatment and by diminishing coordinated Ca2+ activity over a 1 hour treatment. We also evaluated the effect of peripheral blood mononuclear cells (PBMCs) on endothelial permeability and Ca2+ signaling in the HUVEC MPS. HUVECs were co-cultured with PBMCs either directly wherein PBMCs passed through the lumen or indirectly with PBMCs embedded in the supporting collagen hydrogel. We revealed that phytohemagglutinin (PHA)-M activated PBMCs cause endothelial dysfunction in MPS both through increased permeability and decreased coordinated Ca2+ activity compared to non-activated PBMCs. Our MPS has potential applications in modeling cardiovascular disorders and screening for potential treatments using measures of endothelial function.- Published
- 2024
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27. Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells.
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Li J, Zhu J, Gray O, Sobreira DR, Wu D, Huang RT, Miao B, Sakabe NJ, Krause MD, Kaikkonen MU, Romanoski CE, Nobrega MA, and Fang Y
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- Humans, Endothelium, Vascular, Atherosclerosis genetics, Endothelial Cells, Mechanotransduction, Cellular
- Abstract
Vascular homeostasis and pathophysiology are tightly regulated by mechanical forces generated by hemodynamics. Vascular disorders such as atherosclerotic diseases largely occur at curvatures and bifurcations where disturbed blood flow activates endothelial cells while unidirectional flow at the straight part of vessels promotes endothelial health. Integrated analysis of the endothelial transcriptome, the 3D epigenome, and human genetics systematically identified the SNP-enriched cistrome in vascular endothelium subjected to well-defined atherosclerosis-prone disturbed flow or atherosclerosis-protective unidirectional flow. Our results characterized the endothelial typical- and super-enhancers and underscored the critical regulatory role of flow-sensitive endothelial super-enhancers. CRISPR interference and activation validated the function of a previously unrecognized unidirectional flow-induced super-enhancer that upregulates antioxidant genes NQO1, CYB5B, and WWP2, and a disturbed flow-induced super-enhancer in endothelium which drives prothrombotic genes EDN1 and HIVEP in vascular endothelium. Our results employing multiomics identify the cis-regulatory architecture of the flow-sensitive endothelial epigenome related to atherosclerosis and highlight the regulatory role of super-enhancers in mechanotransduction mechanisms., (© 2024 Li et al.)
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- 2024
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28. The difference in endothelium-dependent relaxation components in proximal and distal thoracic aorta regions of male rats.
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Mezhenskyi OR and Philyppov IB
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- Rats, Male, Animals, Rats, Wistar, Endothelium, Vascular, Vasodilation, Aorta, Abdominal, Potassium Channels, Calcium Channels, Aorta, Thoracic, Acetylcholine pharmacology
- Abstract
Aorta, the largest vessel in the body, is generally considered anatomically homogeneous, yet spatial functional differences exist. In our study, we conducted a comprehensive analysis by reexamining public RNA-SEQ data, comparing expression patterns between thoracic and abdominal aorta. Additionally, we measured acetylcholine-induced relaxations of the different regions of thoracic aorta in Wistar Rats. Our results revealed a distinct percentage difference in acetylcholine-induced relaxation in the proximal and distal segments of the thoracic aorta (p = 1.14e-4). To explain this variation, we performed differential expression analysis of previously published RNA-sequencing data between thoracic and abdominal aorta, which showed 497 differentially expressed genes between these locations. From results of RNA-Seq analysis, we draw a hypothesis that differential expressions of the potassium inward rectifying channels (K
IR ) and voltage gated calcium channels (VGCC) presumably located on SMC, with higher expression in the distal thoracic segments in comparison with the proximal thoracic segments of aorta, can explain differences in acetylcholine-induced relaxation. Notably, specific blockade of KIR eliminated differences between the proximal and distal regions of thoracic aorta, underscoring their significance in understanding the spatial nuances in aortic behavior, also blockade of VGCC, shows a higher effect on basal tone, in distal region of thoracic aorta in comparison with proximal., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)- Published
- 2024
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29. Preeclampsia pravastatin early VS late treatment: Effects on oxidative stress and vascular reactivity.
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Ramírez Sanchez FA, Madrigal Aguilar D, Tufiño C, Castro García S, and Bobadilla Lugo RA
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- Pregnancy, Humans, Rats, Female, Animals, Superoxides pharmacology, NADP pharmacology, Rats, Wistar, Oxidative Stress, Phenylephrine pharmacology, Endothelium, Vascular, Pravastatin pharmacology, Pravastatin therapeutic use, Pre-Eclampsia drug therapy
- Abstract
Early diagnosis and efficient treatment of preeclampsia remains a medical challenge and etiological factors converge in a deficient placentation that triggers oxidative stress. There is evidence that statins show antioxidant effects that can improve endothelial function without adverse perinatal effects. We aimed to compare early vs. late pravastatin treatment on the oxidative stress and cardiovascular features of an experimental model of preeclampsia. Female Wistar rats were randomly divided into preeclampsia phenotype rats (PEP) developed by sub renal aortic coarctation (SRAC) and healthy pregnant rats (C). Each group received pravastatin (5 mg/Kg) p.o. either for one week before and during the first week or during the last two weeks of gestation. Blood pressure was determined using the plethysmographic method. Phenylephrine (Phe)-induced contractility was evaluated in isolated thoracic and abdominal aortic rings with or without endothelium. Blood samples were obtained to determine anion superoxide concentration as indicator of NADPH activity. Two-way ANOVA and Bonferroni post hoc tests were used to define statistical significance. Early or late pravastatin treatment decreased hypertension of PEP animals but did not change BP of the healthy pregnant group. Thoracic and abdominal aorta from PEP rats showed increased contractility that was reverted by pravastatin early treatment in endothelium intact rings. Pravastatin did not significantly change contractility neither in the thoracic nor in the abdominal aorta segments from healthy pregnant control rats (C), and decrease anion superoxide concentration by NADPH activity. We conclude pravastatin can improve both blood pressure and endothelium-dependent Phe-induced contractility in an experimental model of preeclampsia by reducing oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)
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- 2024
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30. ASH2L upregulation contributes to diabetic endothelial dysfunction in mice through STEAP4-mediated copper uptake.
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Zhong W, Dong YJ, Hong C, Li YH, Xiao CX, Liu XH, and Chang J
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- Rats, Mice, Animals, Copper metabolism, Copper pharmacology, Up-Regulation, Endothelial Cells metabolism, Epigenesis, Genetic, Cells, Cultured, Glucose metabolism, Endothelium, Vascular, Diabetes Mellitus, Diabetic Angiopathies etiology
- Abstract
Endothelial dysfunction is a common complication of diabetes mellitus (DM) and contributes to the high incidence and mortality of cardiovascular and cerebrovascular diseases. Aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs) play key roles in the initiation and progression of diabetic vascular complications. ASH2L, a H3K4me3 regulator, triggers genetic transcription, which is critical for physiological and pathogenic processes. In this study we investigated the role of ASH2L in mediating diabetic endothelial dysfunction. We showed that ASH2L expression was significantly elevated in vascular tissues from diabetic db/db mice and in rat aortic endothelial cells (RAECs) treated with high glucose medium (11 and 22 mM). Knockdown of ASH2L in RAECs markedly inhibited the deteriorating effects of high glucose, characterized by reduced oxidative stress and inflammatory responses. Deletion of endothelial ASH2L in db/db mice by injection of an adeno-associated virus (AAV)-endothelial specific system carrying shRNA against Ash2l (AAV-shAsh2l) restored the impaired endothelium-dependent relaxations, and ameliorated DM-induced vascular dysfunction. We revealed that ASH2L expression activated reductase STEAP4 transcription in vitro and in vivo, which consequently elevated Cu(I) transportation into ECs by the copper transporter CTR1. Excess copper produced by STEAP4-mediated copper uptake triggered oxidative stress and inflammatory responses, resulting in endothelial dysfunction. Our results demonstrate that hyperglycemia triggered ASH2L-STEAP4 axis contributes to diabetic endothelial dysfunction by modulating copper uptake into ECs and highlight the therapeutic potential of blocking the endothelial ASH2L in the pathogenesis of diabetic vascular complications., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)
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- 2024
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31. Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries.
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Kudryavtseva O, Lyngsø KS, Jensen BL, and Dimke H
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- Mice, Animals, Cricetinae, CHO Cells, Cricetulus, Endothelial Cells metabolism, Endothelium, Vascular, Biological Factors metabolism, Biological Factors pharmacology, Mesenteric Arteries, Vasodilation, Muscle, Smooth, Vascular metabolism, Nitric Oxide metabolism, Magnesium pharmacology, Magnesium metabolism
- Abstract
Aim: Magnesium (Mg
2+ ) is a vasorelaxant. The underlying physiological mechanisms driving this vasorelaxation remain unclear. Studies were designed to test the hypothesis that multiple signaling pathways including nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in endothelial cells as well as Ca2+ antagonization and TRPM7 channels in vascular smooth muscle cells mediate Mg2+ -dependent vessel relaxation., Methods: To uncover these mechanisms, force development was measured ex vivo in aorta rings from mice using isometric wire myography. Concentration responses to Mg2+ were studied in intact and endothelium-denuded aortas. Key findings were confirmed in second-order mesenteric resistance arteries perfused ex vivo using pressure myography. Effects of Mg2+ on NO formation were measured in Chinese Hamster Ovary (CHO) cells, isolated mesenteric vessels, and mouse urine., Results: Mg2+ caused a significant concentration-dependent relaxation of aorta rings. This relaxation was attenuated significantly in endothelium-denuded aortas. The endothelium-dependent portion was inhibited by NO and cGMP blockade but not by cyclooxygenase inhibition. Mg2+ stimulated local NO formation in CHO cells and isolated mesenteric vessels without changing urinary NOx levels. High extracellular Mg2+ augmented acetylcholine-induced relaxation. SKCa and IKCa channel blockers apamin and TRAM34 inhibited Mg2+ -dependent relaxation. The endothelium-independent relaxation in aorta rings was inhibited by high extracellular Ca2+ . Combined blockade of NO, SKCa , and IKCa channels significantly reduced Mg2+ -dependent dilatation in mesenteric resistance vessels., Conclusions: In mouse conductance and resistance arteries Mg2+ -induced relaxation is contributed by endothelial NO formation, EDHF pathways, antagonism of Ca2+ in smooth muscle cells, and additional unidentified mechanisms., (© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)- Published
- 2024
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32. Clinical relevance of endothelial function, oxidative stress and inflammation after smoking cessation.
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Spicuzza L, Morjaria JB, and Polosa R
- Subjects
- Humans, Clinical Relevance, Oxidative Stress, Smoking adverse effects, Inflammation, Endothelium, Vascular, Smoking Cessation
- Published
- 2024
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33. Histamine H 2 -receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II-hypertensive mice.
- Author
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Assersen KB, Jensen BL, Enggaard C, Vanhoutte PM, and Hansen PBL
- Subjects
- Mice, Animals, Angiotensin II pharmacology, Arterial Pressure, Histamine pharmacology, Histamine H2 Antagonists adverse effects, Ranitidine adverse effects, Nitric Oxide, Blood Pressure, Endothelium, Vascular, Mesenteric Arteries, Aldosterone, Hypertension
- Abstract
Aldosterone through the mineralocorticoid receptor MR has detrimental effects on cardiovascular disease. It reduces the bioavailability of nitric oxide and impairs endothelium-dependent vasodilatation. In resistance arteries, aldosterone impairs the sensitivity of vascular smooth muscle cells to nitric oxide by promoting the local secretion of histamine which activates H
2 receptors. The present experiments tested in vivo and ex vivo the hypothesis that systemic H2 -receptor antagonism reduces arterial blood pressure and improves vasodilatation in angiotensin II-induced chronic hypertension. Hypertension was induced by intravenous infusion of angiotensin II (60 ng kg-1 min-1 ) in conscious, unrestrained mice infused concomitantly with the H2 -receptor antagonist ranitidine (27.8 µg kg-1 min-1 ) or vehicle for 24 days. Heart rate and arterial blood pressure were recorded by indwelling arterial catheter. Resistance (mesenteric) and conductance (aortae) arteries were harvested for perfusion myography and isometric tension recordings by wire myography, respectively. Plasma was analyzed for aldosterone concentration. ANGII infusion resulted in elevated arterial blood pressure and while in vivo treatment with ranitidine reduced plasma aldosterone concentration, it did not reduce blood pressure. Ranitidine improved ex vivo endothelial function (acetylcholine 10-9 to 10-6 mol L-1 ) in mesenteric resistance arteries. This was abolished by ex vivo treatment with aldosterone (10-9 mol L-1 , 1 h). In aortic segments, in vivo ranitidine treatment impaired relaxation. Activation of histamine H2 receptors promotes aldosterone secretion, does not affect arterial blood pressure, and protects endothelial function in conduit arteries but promotes endothelial dysfunction in resistance arteries during angiotensin II-mediated hypertension. Aldosterone contributes little to angiotensin II-induced hypertension in mice., (© 2024. The Author(s).)- Published
- 2024
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34. Sitting leg vasculopathy: potential adaptations beyond the endothelium.
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Ferreira-Santos L, Martinez-Lemus LA, and Padilla J
- Subjects
- Humans, Leg blood supply, Posture physiology, Endothelium, Vascular, Lower Extremity blood supply, Vasodilation physiology, Sitting Position, Vascular Diseases
- Abstract
Increased sitting time, the most common form of sedentary behavior, is an independent risk factor for all-cause and cardiovascular disease mortality; however, the mechanisms linking sitting to cardiovascular risk remain largely elusive. Studies over the last decade have led to the concept that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress cause endothelial dysfunction. This conclusion has been mainly supported by studies using flow-mediated dilation in the lower extremities as the measured outcome. In this review, we summarize evidence from classic studies and more recent ones that collectively support the notion that prolonged sitting-induced leg vascular dysfunction is likely also attributable to changes occurring in vascular smooth muscle cells (VSMCs). Indeed, we provide evidence that prolonged constriction of resistance arteries can lead to modifications in the structural characteristics of the vascular wall, including polymerization of actin filaments in VSMCs and inward remodeling, and that these changes manifest in a time frame that is consistent with the vascular changes observed with prolonged sitting. We expect this review will stimulate future studies with a focus on VSMC cytoskeletal remodeling as a potential target to prevent the detrimental vascular ramifications of too much sitting.
- Published
- 2024
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35. Natural diterpenoid EKO activates deubiqutinase ATXN3 to preserve vascular endothelial integrity and alleviate diabetic retinopathy through c-fos/focal adhesion axis.
- Author
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Ge D, Luo T, Sun Y, Liu M, Lyu Y, Yin W, Li R, Zhang Y, Yue H, and Liu N
- Subjects
- Mice, Animals, Endothelium, Vascular, Vinculin, Focal Adhesions, Proto-Oncogene Proteins c-fos, Cell Adhesion Molecules metabolism, Glucose metabolism, Diabetic Retinopathy drug therapy, Diabetic Retinopathy metabolism, Diabetes Mellitus, Experimental metabolism, Hyperglycemia drug therapy, Hyperglycemia metabolism, Epoxy Resins
- Abstract
Diabetic retinopathy (DR) is one of the most prevalent severe diabetic microvascular complications caused by hyperglycemia. Deciphering the underlying mechanism of vascular injury and finding ways to alleviate hyperglycemia induced microvascular complications is of great necessity. In this study, we identified that a compound ent-9α-hydroxy-15-oxo-16-kauren-19-oic acid (EKO), the diterpenoid isolated and purified from Pteris semipinnata L., exhibited good protective roles against vascular endothelial injury associated with diabetic retinopathy in vitro and in vivo. To further uncover the underlying mechanism, we used unbiased transcriptome sequencing analysis and showed substantial impairment in the focal adhesion pathway upon high glucose and IL-1β stimulation. EKO could effectively improve endothelial focal adhesion pathway by enhancing the expression of two focal adhesion proteins Vinculin and ITGA11. We found that c-fos protein was involved in regulating the expression of Vinculin and ITGA11, a transcription factor component that was downregulated by high glucose and IL-1β stimulation and recovered by EKO. Mechanically, EKO facilitated the binding of deubiquitylation enzyme ATXN3 to c-fos protein and promoted its deubiquitylation, thereby elevating its protein level to enhance the expression of Vinculin and ITGA11. Besides, EKO effectively suppressed ROS production and restored mitochondrial function. In vivo studies, we confirmed EKO could alleviate some of the indicators of diabetic mice. In addition, protein levels of ATXN3 and focal adhesion Vinculin molecule were also verified in vivo. Collectively, our findings addressed the endothelial protective role of natural diterpenoid EKO, with emphasize of mechanism on ATXN3/c-fos/focal adhesion signaling pathway as well as oxygen stress suppression, implicating its therapeutic potential in alleviating vascular endothelium injury and diabetic retinopathy., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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36. Novel insights into an old story: Magnesium and vascular tone.
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Maier JA
- Subjects
- Muscle, Smooth, Vascular, Magnesium, Endothelium, Vascular
- Published
- 2024
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37. Hemodynamic regulation allows stable growth of microvascular networks.
- Author
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Qi Y, Chang SS, Wang Y, Chen C, Baek KI, Hsiai T, and Roper M
- Subjects
- Animals, Microvessels, Endothelium, Vascular, Veins, Mechanotransduction, Cellular, Zebrafish
- 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., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2024
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38. Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.
- Author
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Kanaji Y, Ahmad A, Sara JDS, Ozcan I, Akhiyat N, Prasad A, Raphael CE, Kakuta T, Lerman LO, and Lerman A
- Subjects
- Humans, Coronary Circulation, Treatment Outcome, Angina Pectoris, Coronary Vessels diagnostic imaging, Acetylcholine, Endothelium, Vascular, Coronary Angiography, Coronary Artery Disease
- Abstract
Background: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms., Objectives: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA)., Methods: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled. Endothelium-dependent microvascular and epicardial coronary dysfunction were defined as a <50% change in coronary blood flow in response to intracoronary acetylcholine (Ach) infusion and a <-20% change in coronary artery diameter in response to Ach. Endothelium-independent microvascular and epicardial coronary dysfunction were defined as coronary flow reserve < 2.5 during adenosine-induced hyperemia and change in cross-sectional area in response to intracoronary nitroglycerin administration < 20%. Major adverse cardiac and cerebrovascular events (cardiovascular death, nonfatal MI, heart failure, stroke, and late revascularization) served as clinical outcomes., Results: Among the 1,196 patients with ANOCA, the prevalence of CVDys was 24.5% and 51.8% among those with endothelium-independent and endothelium-dependent microvascular dysfunction, respectively, and 47.4% and 25.4% among those with endothelium-independent and endothelium-dependent epicardial coronary dysfunction, respectively. During 6.3 years (Q1-Q3: 2.5-12.9 years) of follow-up, patients with endothelium-dependent microvascular dysfunction, endothelium-dependent epicardial coronary dysfunction, or endothelium-independent microvascular dysfunction showed significantly higher event rates compared with those without (19.5% vs 12.0% [P < 0.001], 19.7% vs 14.6% [P = 0.038] and 22.2% vs 13.8% [P = 0.001], respectively). Coronary flow reserve (HR: 0.757; 95% CI: 0.604-0.957) and percentage change in coronary blood flow in response to Ach infusion (HR: 0.998; 95% CI: 0.996-0.999) remained significant predictors of major adverse cardiac and cerebrovascular event after adjustment for conventional risk factors., Conclusions: CVDys phenotype is differentially associated with worse outcomes, and endothelium-dependent and endothelium-independent microvascular function provide independent prognostic information in patients with ANOCA., Competing Interests: Funding Support and Author Disclosures Dr Lerman is an advisor to AstraZeneca, CureSpec, and Ribocure Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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39. Reply: miRNAs, Endothelin-1 and Endothelial Glycocalyx Disorders in Shock Severity in Postoperative Cardiac Surgery Patients.
- Author
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Roeschl T, Falk V, Schoenrath F, and Meyer A
- Subjects
- Humans, Endothelin-1, Glycocalyx, Endothelium, Vascular, MicroRNAs, Shock, Cardiac Surgical Procedures adverse effects
- Published
- 2024
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- View/download PDF
40. miRNAs, Endothelin-1 and Endothelial Glycocalyx Disorders in Shock Severity in Postoperative Cardiac Surgery Patients.
- Author
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Patanè S, Licordari R, and Venuto P
- Subjects
- Humans, Endothelin-1, Glycocalyx, Endothelium, Vascular, MicroRNAs genetics, Shock, Cardiac Surgical Procedures adverse effects
- Published
- 2024
- Full Text
- View/download PDF
41. Nitric oxide in vascular biology: elegance in complexity.
- Author
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Loscalzo J
- Subjects
- Biology, Vascular Resistance, Nitric Oxide, Endothelium, Vascular
- Published
- 2024
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42. RNAs create a sticky situation.
- Author
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Wong W
- Subjects
- Humans, Cell Adhesion, Endothelium, Endothelium, Vascular, Neutrophils, Inflammation genetics
- Abstract
Glycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.
- Published
- 2024
- Full Text
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43. A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.
- Author
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Price DR and Garcia JGN
- Subjects
- Humans, Endothelial Cells, Lung, Homeostasis, Endothelium, Vascular, Lung Injury, Respiratory Distress Syndrome
- Abstract
Historically considered a metabolically inert cellular layer separating the blood from the underlying tissue, the endothelium is now recognized as a highly dynamic, metabolically active tissue that is critical to organ homeostasis. Under homeostatic conditions, lung endothelial cells (ECs) in healthy subjects are quiescent, promoting vasodilation, platelet disaggregation, and anti-inflammatory mechanisms. In contrast, lung ECs are essential contributors to the pathobiology of acute respiratory distress syndrome (ARDS), as the quiescent endothelium is rapidly and radically altered upon exposure to environmental stressors, infectious pathogens, or endogenous danger signals into an effective and formidable regulator of innate and adaptive immunity. These dramatic perturbations, produced in a tsunami of inflammatory cascade activation, result in paracellular gap formation between lung ECs, sustained lung edema, and multi-organ dysfunction that drives ARDS mortality. The astonishing plasticity of the lung endothelium in negotiating this inflammatory environment and efforts to therapeutically target the aberrant ARDS endothelium are examined in further detail in this review.
- Published
- 2024
- Full Text
- View/download PDF
44. The Mineralocorticoid Receptor in the Vasculature: Friend or Foe?
- Author
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Ibarrola J and Jaffe IZ
- Subjects
- Humans, Ligands, Endothelium, Vascular, Inflammation, Receptors, Mineralocorticoid physiology, Hypotension
- Abstract
Originally described as the renal aldosterone receptor that regulates sodium homeostasis, it is now clear that mineralocorticoid receptors (MRs) are widely expressed, including in vascular endothelial and smooth muscle cells. Ample data demonstrate that endothelial and smooth muscle cell MRs contribute to cardiovascular disease in response to risk factors (aging, obesity, hypertension, atherosclerosis) by inducing vasoconstriction, vascular remodeling, inflammation, and oxidative stress. Extrapolating from its role in disease, evidence supports beneficial roles of vascular MRs in the context of hypotension by promoting inflammation, wound healing, and vasoconstriction to enhance survival from bleeding or sepsis. Advances in understanding how vascular MRs become activated are also reviewed, describing transcriptional, ligand-dependent, and ligand-independent mechanisms. By synthesizing evidence describing how vascular MRs convert cardiovascular risk factors into disease (the vascular MR as a foe), we postulate that the teleological role of the MR is to coordinate responses to hypotension (the MR as a friend).
- Published
- 2024
- Full Text
- View/download PDF
45. Tsantan Sumtang, a traditional Tibetan medicine, protects pulmonary vascular endothelial function of hypoxia-induced pulmonary hypertension rats through AKT/eNOS signaling pathway.
- Author
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Li N, Su S, Xie X, Yang Z, Li Z, and Lu D
- Subjects
- Rats, Animals, Proto-Oncogene Proteins c-akt metabolism, Rats, Sprague-Dawley, Medicine, Tibetan Traditional methods, Endothelial Cells metabolism, Endothelium, Vascular, Nitric Oxide Synthase Type III metabolism, Signal Transduction, Hypoxia complications, Hypoxia drug therapy, Hypoxia metabolism, Phosphatidylinositol 3-Kinases metabolism, Lung metabolism, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary etiology, Hypertension, Pulmonary prevention & control
- Abstract
Ethnopharmacological Relevance: Tsantan Sumtang (TS), originated from the Four Tantras, is an empirical Tibetan medicine prescription, which has been widely used for treating cardiovascular diseases in the clinic in Qinghai Province of China. Our previous studies found that TS alleviated hypoxia-induced pulmonary hypertension (HPH) in rats. However, the effect and bioactive fractions of TS on hypoxia-injured pulmonary vascular endothelium are unknown., Aim of the Study: To investigate the effect, bioactive fractions and pharmacological mechanism of TS on hypoxia-injured pulmonary vascular endothelium in vivo and in vitro., Materials and Methods: In vivo studies, HPH animal model was established, and TS was administrated for four weeks. Then, hemodynamic indexes, ex vivo pulmonary artery perfusion experiment, morphological characteristics, nitric oxide (NO) production, and the protein expression of protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK)/eNOS signaling were determined. In vitro studies, 1% O
2 -induced pulmonary artery endothelial cells (PAECs) injury model was applied for screening bioactive fractions of TS by cell proliferation assay and NO production measurement. The associated proteins of AKT/eNOS signaling were further measured to elucidate underlying mechanism of bioactive fraction of TS via using phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002. Ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS) was used to reveal the chemical profile of bioactive fraction of TS., Results: TS showed protective effect on the integrity of distal pulmonary arterial endothelium in HPH rats. Tsantan Sumtang dilated pulmonary arterial rings in HPH rats. TS enhanced NO bioavailability in lung tissue via regulating AKT/eNOS signaling. Furthermore, in the cellular level, cell viability as well as NO content of hypoxia-injured PAECs were elevated by fraction 17 of water extract of TS (WTS), through activating the AKT/eNOS signaling. Ellagic acid could be one of compositions in fraction 17 of WTS to produce NO in hypoxia-injured PAECs., Conclusion: TS restored pulmonary arterial endothelial function in HPH rats. The bioactive fraction 17 was screened, which protected hypoxia-injured PAECs via upregulating AKT/eNOS signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
46. A mechanical modeling framework to study endothelial permeability.
- Author
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Keshavanarayana P and Spill F
- Subjects
- Humans, Cadherins metabolism, Actin Cytoskeleton metabolism, Thrombin metabolism, Permeability, Capillary Permeability physiology, Cells, Cultured, Endothelial Cells, Endothelium, Vascular
- Abstract
The inner lining of blood vessels, the endothelium, is made up of endothelial cells. Vascular endothelial (VE)-cadherin protein forms a bond with VE-cadherin from neighboring cells to determine the size of gaps between the cells and thereby regulate the size of particles that can cross the endothelium. Chemical cues such as thrombin, along with mechanical properties of the cell and extracellular matrix are known to affect the permeability of endothelial cells. Abnormal permeability is found in patients suffering from diseases including cardiovascular diseases, cancer, and COVID-19. Even though some of the regulatory mechanisms affecting endothelial permeability are well studied, details of how several mechanical and chemical stimuli acting simultaneously affect endothelial permeability are not yet understood. In this article, we present a continuum-level mechanical modeling framework to study the highly dynamic nature of the VE-cadherin bonds. Taking inspiration from the catch-slip behavior that VE-cadherin complexes are known to exhibit, we model the VE-cadherin homophilic bond as cohesive contact with damage following a traction-separation law. We explicitly model the actin cytoskeleton and substrate to study their role in permeability. Our studies show that mechanochemical coupling is necessary to simulate the influence of the mechanical properties of the substrate on permeability. Simulations show that shear between cells is responsible for the variation in permeability between bicellular and tricellular junctions, explaining the phenotypic differences observed in experiments. An increase in the magnitude of traction force due to disturbed flow that endothelial cells experience results in increased permeability, and it is found that the effect is higher on stiffer extracellular matrix. Finally, we show that the cylindrical monolayer exhibits higher permeability than the planar monolayer under unconstrained cases. Thus, we present a contact mechanics-based mechanochemical model to investigate the variation in the permeability of endothelial monolayer due to multiple loads acting simultaneously., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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47. Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR-155-5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels.
- Author
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Zhao M, Lei J, Deng F, Zhao C, Xu T, Ji B, Fu M, Wang X, Sun M, Zhang M, and Gao Q
- Subjects
- Animals, Female, Male, Pregnancy, Rats, Acetylcholine pharmacology, Endothelial Cells metabolism, Endothelium, Vascular, Hypoxia, NADPH Oxidases metabolism, Nitric Oxide metabolism, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, MicroRNAs genetics, MicroRNAs metabolism, NADPH Oxidase 2
- Abstract
Background: Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid-late pregnancy, it is urgent to further explore whether it affects the long-term synthesis of NO in offspring vascular endothelial cells., Methods and Results: Pregnant Sprague-Dawley rats were housed in a normoxic or hypoxic (10.5% O
2 ) chamber from gestation days 10 to 20. The thoracic aortas of fetal and adult male offspring were isolated for experiments. Gestational hypoxia significantly reduces the NO-dependent vasodilation mediated by acetylcholine in both the fetal and adult offspring thoracic aorta rings. Meanwhile, acetylcholine-induced NO synthesis is impaired in vascular endothelial cells from hypoxic offspring thoracic aortas. We demonstrate that gestational hypoxic offspring exhibit a reduced endothelial NO synthesis capacity, primarily due to increased expression of NADPH oxidase 2 and enhanced reactive oxygen species. Additionally, gestational hypoxic offspring show elevated levels of miR-155-5p in vascular endothelial cells, which is associated with increased expression of NADPH oxidase 2 and reactive oxygen species generation, as well as impaired NO synthesis., Conclusions: The present study is the first to demonstrate that gestational hypoxia impairs endothelial NO synthesis via the miR-155-5p/NADPH oxidase 2/reactive oxygen species axis in offspring vessels. These novel findings indicate that the detrimental effects of gestational hypoxia on fetal vascular function can persist into adulthood, providing new insights into the development of vascular diseases.- Published
- 2024
- Full Text
- View/download PDF
48. N-phenyl and N-benzyl substituted succinimides: Preclinical evaluation for their antihypertensive effect and underlying mechanism.
- Author
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Qayyum MI, Ullah S, Rashid U, Sadiq A, Mahnashi MH, Khalil SUK, and Akhtar MM
- Subjects
- Rats, Animals, Vasodilation, Nifedipine pharmacology, Endothelium, Vascular, Vasodilator Agents pharmacology, Aorta, Thoracic, Dose-Response Relationship, Drug, Antihypertensive Agents pharmacology, Aldehydes pharmacology
- Abstract
The study was designed to investigate the antihypertensive potential of 2-(2, 5-dioxo-1-phenylpyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (Comp-1) and 2-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (Succ-5) in rats. The study results showed that, just like nifedipine (the standard reference drug), the test compounds, Comp-1 (at doses of 15 and 20 mg/kg) and Succ-5 (at a dose of 20 mg/kg) had significant antihypertensive effect against deoxycorticosterone acetate-salted rats. The test compounds maintained the level of cardiac markers troponin I and creatinine kinase myocardial bands (CK-MB) in serum, and modulate the oxidative stress markers Glutathione s-transferase (GST) activity, reduced glutathione (GSH), catalase levels, and lipid peroxidation (LPO). These compounds also reduced the expression of inflammatory markers, including cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-α) in heart tissues. Furthermore, in the ex-vivo study, the test substances relaxed the contractions induced by phenylephrine (PE) and potassium (K
+ ). Vasodilation was endothelium-independent because the test substances showed nearly the same effect in aortic rings with intact endothelium, denuded endothelium, and with L-NAME pretreatment. The test compounds shifted the calcium curve to the right, i.e., contraction was inhibited and decreased the maximal response. This study demonstrated the antihypertensive, anti-inflammatory, antioxidant, and vasodilate effects of the test compounds. In addition, the results supported the phenomenon of calcium channel blockades responsible for vasodilation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
49. A Review of Radiation-Induced Vascular Injury and Clinical Impact.
- Author
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Kameni LE, Januszyk M, Berry CE, Downer MA Jr, Parker JB, Morgan AG, Valencia C, Griffin M, Li DJ, Liang NE, Momeni A, Longaker MT, and Wan DC
- Subjects
- Male, Humans, Endothelium, Vascular, Breast pathology, Radiotherapy adverse effects, Vascular System Injuries etiology, Radiation Injuries etiology, Neoplasms complications
- Abstract
Abstract: The number of cancer survivors continues to increase because of advances in therapeutic modalities. Along with surgery and chemotherapy, radiotherapy is a commonly used treatment modality in roughly half of all cancer patients. It is particularly helpful in the oncologic treatment of patients with breast, head and neck, and prostate malignancies. Unfortunately, among patients receiving radiation therapy, long-term sequalae are often unavoidable, and there is accumulating clinical evidence suggesting significant radiation-related damage to the vascular endothelium. Ionizing radiation has been known to cause obliterative fibrosis and increased wall thickness in irradiated blood vessels. Clinically, these vascular changes induced by ionizing radiation can pose unique surgical challenges when operating in radiated fields. Here, we review the relevant literature on radiation-induced vascular damage focusing on mechanisms and signaling pathways involved and highlight microsurgical anastomotic outcomes after radiotherapy. In addition, we briefly comment on potential therapeutic strategies, which may have the ability to mitigate radiation injury to the vascular endothelium., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
50. Black Soybean Seed Coat Extract Improves Endothelial Function and Upregulates Oxidative Stress Marker Expression in Healthy Volunteers by Stimulating Nitric Oxide Production in Endothelial Cells.
- Author
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Akagi R, Nanba F, Saito S, Maruo T, Toda T, Yamashita Y, Ashida H, and Suzuki T
- Subjects
- Humans, Animals, Cattle, Glycine max, Anthocyanins metabolism, Healthy Volunteers, Endothelium, Vascular, Oxidative Stress, Nitric Oxide Synthase Type III genetics, Nitric Oxide Synthase Type III metabolism, RNA, Messenger metabolism, Cells, Cultured, Endothelial Cells, Nitric Oxide metabolism
- Abstract
Black soybean seed coat extract (BE) contains multiple bioactive polyphenols, including flavan-3-ols and anthocyanins. BE improves endothelial function; however, it is unclear whether BE protects endothelial cells from senescence. In this study, we examined the effects of BE on endothelial cell senescence and vascular function in healthy individuals. High concentrations of glucose were used to induce senescence in bovine aortic endothelial cells incubated with BE. Senescence, vascular function, and oxidative stress markers were measured. Incubation with BE remarkably inhibited senescence-associated β -galactosidase and lactate dehydrogenase activities and dose dependently reduced intracellular reactive oxygen species levels in bovine aortic endothelial cells. BE treatment increased the levels of endothelial nitric oxide synthase (eNOS) mRNA and endothelial nitric oxide (NO) metabolites and increased the mRNA expression of klotho , a gene associated with an antiaging phenotype. To examine the effects of BE in humans, we conducted a clinical study using the second derivative of the fingertip photoplethysmogram to investigate vascular function and aging in 24 healthy volunteers. The participants consumed BE supplements (100 mg/day) or a placebo for 2 weeks. When compared with the placebo group, the BE group showed considerably improved vascular function, NO metabolite levels, and oxidative stress. These results suggest that BE supplementation improves endothelial function, possibly through antioxidant activity and NO production, and may consequently reduce the cardiovascular risk associated with aging. BE supplementation may be an effective and safe approach to reduce the risk of atherosclerosis and cardiovascular disease; however, additional studies investigating chronic vascular inflammation are needed.
- Published
- 2024
- Full Text
- View/download PDF
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