30,081 results on '"ANGIOTENSIN II"'
Search Results
2. Balance of Angiotensin II Receptors in Vessel Function After Preeclampsia
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Anna Stanhewicz, PhD, Assistant Professor
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- 2024
3. Angiotensin-(1-7) in Peripheral Arterial Disease
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Amy Arnold, Associate Professor
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- 2024
4. Angiotensin II in General Anesthesia
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- 2024
5. Intravenous AII for the Treatment of Severe Hypotension in High Output Shock: A Pilot Study (ATHOS)
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- 2024
6. Efficacy and Safety of Angiotensin II Injection Versus Placebo in Patients With Refractory Distributed Shock
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- 2024
7. Therapeutic Drug Use for CKD Patients
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Xiao Li,MD, Associate professor of pharmacy
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- 2024
8. Angiotensin II vs. Vasopressin in Septic Shock
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La Jolla Pharmaceutical Company and National Center for Advancing Translational Sciences (NCATS)
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- 2024
9. Angiotensin 2 for Hepatorenal Syndrome (ANTHEM)
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- 2024
10. Development and Validation of the Prediction Model for Functional Mitral Regurgitation Regression in Heart Failure Patients Taking Guideline-directed Medical Therapy
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- 2024
11. The COVID-RASi Trial (COVID-19)
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- 2024
12. Metabolic Effects of Angiotensin-(1-7)
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Italo Biaggioni, Professor
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- 2024
13. The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock (REPERFUSE)
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European Society of Intensive Care Medicine and Royal Centre for Defence Medicine
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- 2024
14. Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)
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National Institute on Aging (NIA), Texas Health Resources, Michigan State University, and Rong Zhang, Professor of Medicine
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- 2024
15. HF Assessment With BNP in the Home: Part II (HABIT-II)
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- 2024
16. Influence of angiotensin II and telmisartan on in vivo high‐resolution renal arterial impedance in rats.
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Fukuda, Yukiko, Kawada, Toru, Kataoka, Yasuyuki, Peterson, Jon, Saku, Keita, Alexander Jr., Joe, and Sunagawa, Kenji
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Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high‐resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three‐element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10−1) min·mL−1. ANG II significantly increased the slope by 0.72 ± 0.29 (× 10−1) min·mL−1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10−1) mmHg·min·mL−1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10−1) mmHg·min·mL−1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANG II or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature. NEW & NOTEWORTHY: This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Articles You Might Have Missed.
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Sanders, Taylor, McKee, D. Lynne, and Jackson, E. Mason
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POISONS , *LEAD exposure , *ALCOHOLISM , *DRUG overdose , *ACUTE kidney failure , *BENZODIAZEPINES , *MARIJUANA growing , *POSITIVE pressure ventilation - Abstract
Article #1 discusses a clinical trial that examined the effects of delaying intubation in comatose patients with acute poisoning. The study found that delaying intubation was safe and resulted in lower rates of ICU admission and complications. However, the lack of deaths suggests that more research is needed, particularly involving confirmed overdoses. Article #2 explores lead exposure in veterinary workers who handle lead shielding during radiography. The study found that the use of lead shielding is associated with lead exposure, but wearing disposable gloves can significantly reduce this exposure. However, the study had limitations, such as potential bias from the questionnaire and the lack of evaluation of hand washing. Article #3 focuses on the use of angiotensin II (AT2) for treating refractory shock. While AT2 has shown improvement in blood pressures, its impact on mortality is still unclear. The study aims to determine if adding AT2 improves 30-day mortality in patients with severe, refractory shock. However, the study is retrospective and underpowered, so further research is needed to establish its effectiveness. The study found that there was no significant difference in mortality between the AT2 group and the control group, and baseline characteristics differed between the two groups. Overall, the study concluded that AT2 was not associated with improved mortality or organ dysfunction in patients with severe shock. [Extracted from the article]
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- 2024
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18. Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy.
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Nagasawa, Hajime, Ueda, Seiji, Suzuki, Hitoshi, Jenkinson, Celia, Fukao, Yusuke, Nakayama, Maiko, Otsuka, Tomoyuki, Okuma, Teruyuki, Clapper, Wilmelenne, Liu, Kai, Nguyen, Mai, Komers, Radko, and Suzuki, Yusuke
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ENDOTHELIN receptors , *CLINICAL trials , *ANGIOTENSIN II , *IGA glomerulonephritis , *ANGIOTENSIN receptors - Abstract
Background The mechanism leading to the development of immunoglobulin A nephropathy (IgAN) remains to be completely understood. Endothelin-1 (ET-1) as well as angiotensin II (AngII) promote glomerular injury, tubulointerstitial inflammation and fibrosis leading to chronic kidney disease. Sparsentan, a dual endothelin angiotensin receptor antagonist, recently received accelerated approval in the USA for the reduction of proteinuria in adults with IgAN at high risk of disease progression. To elucidate the mechanisms by which sparsentan is efficacious in IgAN, we examined the effect of treatment in gddY mice, a spontaneous IgAN mouse model, versus the monoselective angiotensin II type 1 receptor (AT1R) antagonist, losartan, on the development of renal injury at doses resulting in similar blood pressure lowering. Methods Four-week-old gddY mice were given control chow, chow containing sparsentan or drinking water containing losartan until 12 or 20 weeks old. Results Remarkably, the albumin:creatine ratio (ACR) was attenuated more rapidly and to a greater extent in mice treated with sparsentan than those treated with losartan. The decrease in ACR from baseline after 4 weeks of treatment correlated with beneficial effects of sparsentan on glomerulosclerosis and protection of podocytes and glycocalyx after 16 weeks of treatment across treatment groups; thus, sparsentan treatment delayed development of renal injury to a greater extent than losartan. Expression of mRNA for ET-1, endothelin type A receptor and AT1R and proinflammatory genes was upregulated in 12-week-old gddY mice and was prevented by sparsentan and losartan to a comparable extent. Conclusions The results of this study, and in light of the results of the phase 3 PROTECT trial, provide a novel perspective and understanding of the mechanisms by which sparsentan has a beneficial renoprotective effect against IgAN compared with AT1R antagonism alone. [ABSTRACT FROM AUTHOR]
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- 2024
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19. HIF‐1α and adaptor protein LIM and senescent cell antigen‐like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II‐induced hypertension.
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Ni, Wei‐Jie, Li, Zuo‐Lin, Wen, Xian‐Li, Ji, Jia‐Ling, Liu, Hong, Yin, Qing, Jiang, Liang‐Yun‐Zi, Zhang, Yi‐Lin, Wen, Yi, Tang, Tao‐Tao, Jiang, Wei, Lv, Lin‐Li, Gan, Wei‐Hua, Liu, Bi‐Cheng, and Wang, Bin
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RENAL fibrosis , *PROTEIN domains , *CHRONIC kidney failure , *ADAPTOR proteins , *KNOCKOUT mice , *ANGIOTENSIN II - Abstract
Background and Purpose: Activation of the renin‐angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen‐like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)‐induced hypertension and tubulointerstitial fibrosis was investigated. Experimental Approach: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) renal tubular‐specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II‐induced renal interstitial fibrosis. In vitro, HIF‐1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. Key Results: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II‐induced hypertension model. Tubular‐specific knockdown of LIMS1 ameliorated Ang II‐induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF‐1α in tubular cells and that tubular HIF‐1α knockout ameliorates LIMS1‐mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II‐induced tubulointerstitial fibrosis by interacting with vimentin. Conclusion and Implications: We conclude that HIF‐1α transcriptionally regulated LIMS1 plays a central role in Ang II‐induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II‐induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Angiotensin II treatment of hypotension in noncardiac surgery: an initial dose-finding study.
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Fernando, Rohesh J., Royster, Roger L., Ferrario, Carlos M., Saha, Amit K., Ahmad, Sarfaraz, Henshaw, Daryl S., Kittner, Sarah L., Talbott, Ashley L., Khanna, Ashish K., Morris, Benjamin N., Groban, Leanne, and Templeton, Thomas W.
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ANGIOTENSIN II , *HYPOTENSION , *SURGERY - Published
- 2024
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21. Antihypertensive Effects of Lindera erythrocarpa Makino via NO/cGMP Pathway and Ca 2+ and K + Channels.
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Shin, Sujin, Park, Junkyu, Choi, Ho-Young, Bu, Youngmin, and Lee, Kyungjin
- Abstract
Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague–Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved were evaluated by treating specific inhibitors or activators that affect the contractility of blood vessels. Our results revealed that LEL promotes a vasorelaxant effect through the nitric oxide/cyclic guanosine 3′,5′-monophosphate pathway, blocking the Ca
2+ channels, opening the K+ channels, and inhibiting the vasoconstrictive action of angiotensin II. In addition, the effects of LEL on blood pressure were investigated in spontaneously hypertensive rats by the tail-cuff method. LEL (300 or 1000 mg/kg) was orally administered to the rats, and 1000 mg/kg of LEL significantly lowered the blood pressure. Systolic blood pressure decreased by −20.06 ± 4.87%, and diastolic blood pressure also lowered by −30.58 ± 5.92% at 4 h in the 1000 mg/kg LEL group. Overall, our results suggest that LEL may be useful to treat hypertensive diseases, considering its vasorelaxing and hypotensive effects. [ABSTRACT FROM AUTHOR]- Published
- 2024
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22. Mammalian Target of Rapamycin Inhibition Decreases Angiotensin II-Induced Steroidogenesis in HAC15 Human Adrenocortical Carcinoma Cells.
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Ali, Yusuf, Gomez-Sanchez, Elise P, and Gomez-Sanchez, Celso E
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STEROIDOGENIC acute regulatory protein ,PROTEIN kinase B ,RIBOSOMAL proteins ,MTOR protein ,ADAPTOR proteins - Abstract
Background Mammalian target of rapamycin (mTOR) inhibitors suppress adrenal cortical carcinoma cell proliferation and cortisol production; the relationship between mTOR and aldosterone production has not been examined. Methods HAC15 cells were incubated with an mTOR activator and several inhibitors including AZD8055 (AZD) in the presence and absence of angiotensin II (AngII). The expression of rapamycin-sensitive adapter protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (Rictor), adaptor proteins of mTOR complex 1 and 2, respectively, were studied in the HAC15 cells and deleted by CRISPR/gRNA. Results The mTOR inhibitors decreased aldosterone induced by AngII. Inhibition of mTOR by AZD significantly suppressed AngII-induced aldosterone and cortisol formation in a dose-dependent manner, whereas the mTOR activator MHY had no effect. AZD did not alter forskolin-induced aldosterone production showing that it is specific to the AngII signaling pathway. AngII-mediated ERK and mTOR activation were suppressed by AZD, along with a concomitant dose-dependent reduction of AngII-induced steroidogenic enzymes including steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase-type 2, CYP17A1, and aldosterone synthase protein. Furthermore, mTOR components ribosomal protein S6 kinase (P70S6K) and protein kinase B phosphorylation levels were decreased by AZD. As mTOR exerts its main effects by forming complexes with adaptor proteins Raptor and Rictor, the roles of these individual complexes were studied. We found an increase in the phosphorylation of Raptor and Rictor by AngII and that their CRISPR/gRNA-mediated knockdown significantly attenuated AngII-induced aldosterone and cortisol production. Conclusion mTOR signaling has a critical role in transducing the AngII signal initiating aldosterone and cortisol synthesis in HAC15 cells and that inhibition of mTOR could be a therapeutic option for conditions associated with excessive renin–angiotensin system-mediated steroid synthesis. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Sox17 protects human brain microvascular endothelial cells from AngII-induced injury by regulating autophagy and apoptosis.
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Wang, Yanyan, Fang, Marong, Ren, Qiannan, Qi, Wei, Bai, Xinli, Amin, Nashwa, Zhang, Xiangjian, Li, Zhenzhong, and Zhang, Lihong
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Intracranial aneurysm (IA), is a localized dilation of the intracranial arteries, the rupture of which is catastrophic. Hypertension is major IA risk factor that mediates endothelial cell damage. Sox17 is highly expressed in intracranial vascular endothelial cells, and GWAS studies indicate that its genetic alteration is one of the major genetic risk factors for IA. Vascular endothelial cell injury plays a vital role in the pathogenesis of IA. The genetic ablation of Sox17 plus hypertension induced by AngII can lead to an increased incidence of intracranial aneurysms had tested in the previous animal experiments. In order to study the underlying molecular mechanisms, we established stable Sox17-overexpressing and knockdown cell lines in human brain microvascular endothelial cells (HBMECs) first. Then flow cytometry, western blotting, and immunofluorescence were employed. We found that the knockdown of Sox17 could worsen the apoptosis and autophagy of HBMECs caused by AngII, while overexpression of Sox17 had the opposite effect. Transmission electron microscopy displayed increased autophagosomes after the knockdown of Sox17 in HBMECs. The RNA-sequencing analysis shown that dysregulation of the Sox17 gene was closely associated with the autophagy-related pathways. Our study suggests that Sox17 could protect HBMECs from AngII-induced injury by regulating autophagy and apoptosis. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Reinventing the renin–angiotensin–aldosterone system based on experience from the COVID‐19 pandemic.
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Kurbel, Sven
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SCIENCE education , *CELL receptors , *PRORENIN receptor , *COVID-19 pandemic , *RENIN-angiotensin system , *ANGIOTENSIN II , *HYPERTENSIVE crisis , *HYPERKALEMIA - Abstract
This article explores the renin-angiotensin-aldosterone system (RAAS) and its relevance to the COVID-19 pandemic. It emphasizes the need to understand the different components of the RAAS, such as ACE2, beyond their vasoconstrictive actions. The article proposes a simplified model of the RAAS and examines the interactions among its various components. It also discusses the protective functions of the RAAS, including tissue protection and prevention of hypovolemia. The article concludes by presenting a trifurcation model of the RAAS, suggesting three separate branches with distinct circulatory functions. The text suggests that further research is necessary to fully comprehend the implications of medications that affect the RAAS in the context of SARS-CoV-2 infection. [Extracted from the article]
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- 2024
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25. Neutrophil extracellular trap-induced ferroptosis promotes abdominal aortic aneurysm formation via SLC25A11-mediated depletion of mitochondrial glutathione.
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Qi, Yanqing, Chen, Liang, Ding, Shanshan, Shen, Xiaowei, Wang, Zhifang, Qi, Haozhe, and Yang, Shuofei
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ABDOMINAL aortic aneurysms , *CARRIER proteins , *GLUTATHIONE , *ANGIOTENSIN II , *MITOCHONDRIAL proteins , *MITOCHONDRIA , *POLYACRYLAMIDE gel electrophoresis - Abstract
Neutrophil extracellular traps (NETs) induce oxidative stress, which may initiate ferroptosis, an iron-dependent programmed cell death, during abdominal aortic aneurysm (AAA) formation. Mitochondria regulate the progression of ferroptosis, which is characterized by the depletion of mitochondrial glutathione (mitoGSH) levels. However, the mechanisms are poorly understood. This study examined the role of mitoGSH in regulating NET-induced ferroptosis of smooth muscle cells (SMCs) during AAA formation. Concentrations of NET markers were tested in plasma samples. Western blotting and immunofluorescent staining were performed to detect the expression and localization of NET and ferroptosis markers in tissue samples. The role of NETs and SMC ferroptosis during AAA formation was investigated using peptidyl arginine deiminase 4 gene (Padi4) knockout or treatment with a PAD4 inhibitor, ferroptosis inhibitor or activator in an angiotensin II-induced AAA mouse model. The regulatory effect of SLC25A11, a mitochondrial glutathione transporter, on mitoGSH and NET-induced ferroptosis of SMCs was investigated using in vitro and in vivo experiments. Transmission electron microscopy was used to detect mitochondrial damage. Blue native polyacrylamide gel electrophoresis was used to analyze the dimeric and monomeric forms of the protein. Significantly elevated levels of NETosis and ferroptosis markers in aortic tissue samples were observed during AAA formation. Specifically, NETs promoted AAA formation by inducing ferroptosis of SMCs. Subsequently, SLC25A11 was identified as a potential biomarker for evaluating the clinical prognosis of patients with AAA. Furthermore, NETs decreased the stability and dimerization of SLC25A11, leading to the depletion of mitoGSH. This depletion induced the ferroptosis of SMCs and promoted AAA formation. During AAA formation, NETs regulate the stability of the mitochondrial carrier protein SLC25A11, leading to the depletion of mitoGSH and subsequent activation of NET-induced ferroptosis of SMCs. Preventing mitoGSH depletion and ferroptosis in SMCs is a potential strategy for treating AAA. A schematic diagram of main findings. NETs induce iron-mediated cell death in SMCs during AAA formation, accompanied by mitochondrial dysfunction. Mechanistically, NETs modulate the stability of the mitochondrial carrier protein SLC25A11, leading to depletion of mitoGSH in SMCs. The stability of mitochondrial carrier protein SLC25A11 results in depletion of mitoGSH in SMCs, which in turn induces iron dysregulation in SMCs and promotes AAA formation. These findings propose several potential targets for the development of novel therapeutics for AAA treatment, including inhibition of NETs formation, mitigation of mitoGSH depletion, and suppression of SMC ferroptosis. [Display omitted] • During AAA formation, NETs regulate the stability of the mitochondrial carrier protein SLC25A11. • SLC25A11 regulated the depletion of mitochondrial glutathione and activation of NET-induced ferroptosis of SMCs. • Preventing mitoGSH depletion and ferroptosis in SMCs is a potential strategy for treating AAA. [ABSTRACT FROM AUTHOR]
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- 2024
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26. NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4‐ANXA2 Interaction and Enhancing Macrophage Infiltration.
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Wu, Zhaoyu, Xu, Zhijue, Pu, Hongji, Ding, Ang'ang, Hu, Jiateng, Lei, Jiahao, Zeng, Chenlin, Qiu, Peng, Qin, Jinbao, Wu, Xiaoyu, Li, Bo, Wang, Xin, and Lu, Xinwu
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ABDOMINAL aortic aneurysms , *MACROPHAGES , *NERVE tissue proteins , *ANGIOTENSIN II , *PROTEIN-protein interactions - Abstract
Abdominal aortic aneurysm (AAA) is a common and potentially life‐threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury‐induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)‐induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2‐Cre mice on an ApoE−/− background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro‐inflammatory responses. Bulk RNA‐sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF‐κB/CCR2 signaling pathway. Protein‐protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro‐inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA. [ABSTRACT FROM AUTHOR]
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- 2024
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27. The use of angiotensin II for the management of distributive shock: expert consensus statements.
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Landoni, Giovanni, Cortegiani, Andrea, Bignami, Elena, De Pascale, Gennaro, Donadello, Katia, Donati, Abele, Grasselli, Giacomo, Guarracino, Fabio, Monti, Gianpaola, Paternoster, Gianluca, Tritapepe, Luigi, and Girardis, Massimo
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LITERATURE reviews ,ANGIOTENSIN II ,SEPTIC shock ,ANGIOTENSIN converting enzyme ,DELPHI method - Abstract
Background: Despite the growing body of evidence supporting the use of angiotensin II (ATII) in distributive shock, its integration into existing treatment algorithms requires careful consideration of factors related to patient comorbidities, hemodynamic parameters, cost-effectiveness, and risk–benefit balance. Moreover, several questions regarding its use in clinical practice warrant further investigations. To address these challenges, a group of Italian intensive care specialists (the panel) developed a consensus process using a modified Delphi technique. Methods: The panel defined five clinical questions during an online scoping workshop and then provided a short list of statements related to each clinical question based on literature review and clinical experience. A total of 20 statements were collected. Two coordinators screened and selected the final list of statements to be included in the online survey, which consisted of 17 statements. The consensus was reached when ≥ 75% of respondents assigned a score within the 3-point range of 1–3 (disagreement) or 7–9 (agreement). Results: Overall, a consensus on agreement was reached on 13 statements defining the existing gaps in scientific evidence, the possibility of evaluating the addition of drugs with different mechanisms of action for the treatment of refractory shock, the utility of ATII in reducing the catecholamine requirements in the treatment of vasopressor-resistant septic shock, and the effectiveness of ATII in treating patients in whom angiotensin-converting enzyme activity is reduced or pharmacologically blocked. It was widely shared that renin concentration can be used to identify patients who most likely benefit from ATII to restore vascular tone. Thus, the patients who might benefit most from using ATII were defined. Lastly, some potential barriers to the use of ATII were described. Conclusions: ATII was recognized as a useful treatment to reduce catecholamine requirements in treating vasopressor-resistant septic shock. At the same time, the need for additional clinical trials to further elucidate the efficacy and safety of ATII, as well as investigations into potential mechanisms of action and optimization of treatment protocols in patients with refractory distributive shock, emerged. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Discovery of an embryonically derived bipotent population of endothelial-macrophage progenitor cells in postnatal aorta.
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Williamson, Anna E., Liyanage, Sanuri, Hassanshahi, Mohammadhossein, Dona, Malathi S. I., Toledo-Flores, Deborah, Tran, Dang X. A., Dimasi, Catherine, Schwarz, Nisha, Fernando, Sanuja, Salagaras, Thalia, Long, Aaron, Kazenwadel, Jan, Harvey, Natasha L., Drummond, Grant R., Vinh, Antony, Chandrakanthan, Vashe, Misra, Ashish, Neufeld, Zoltan, Tan, Joanne T. M., and Martelotto, Luciano
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PROGENITOR cells ,YOLK sac ,ENDOTHELIAL cells ,BONE marrow ,ANGIOTENSIN II - Abstract
Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX
3 CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally. The extraembryonic yolk sac is a major location for developmental hematopoiesis, but it is unclear whether non-bone marrow sources contribute during adulthood. Here they show that embryonically derived endothelial-macrophage progenitor cells located in the aorta are a bipotent source of macrophage and endothelial cells later in life. [ABSTRACT FROM AUTHOR]- Published
- 2024
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29. A new animal model of cardiorenal syndrome could be established by inducing heart failure through coronary artery ligation in spontaneously hypertensive rats.
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Zhou, Biye, Zhao, Jinbao, and Li, Dong
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LIPOCALIN-2 , *BRAIN natriuretic factor , *CARDIO-renal syndrome , *CYSTATIN C , *ANGIOTENSIN II , *GLUTATHIONE peroxidase - Abstract
In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Phosphorylation patterns in the AT1R C-terminal tail specify distinct downstream signaling pathways.
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Gareri, Clarice, Pfeiffer, Conrad T., Jiang, Xue, Paulo, Joao A., Gygi, Steven P., Pham, Uyen, Chundi, Anand, Wingler, Laura M., Staus, Dean P., Stepniewski, Tomasz Maciej, Selent, Jana, Lucero, Emilio Y., Grogan, Alyssa, Rajagopal, Sudarshan, and Rockman, Howard A.
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G proteins ,ANGIOTENSIN II ,MOLECULAR dynamics ,LIGANDS (Biochemistry) ,G protein coupled receptors ,PHOSPHORYLATION - Abstract
Different ligands stabilize specific conformations of the angiotensin II type 1 receptor (AT1R) that direct distinct signaling cascades mediated by heterotrimeric G proteins or β-arrestin. These different active conformations are thought to engage distinct intracellular transducers because of differential phosphorylation patterns in the receptor C-terminal tail (the "barcode" hypothesis). Here, we identified the AT1R barcodes for the endogenous agonist AngII, which stimulates both G protein activation and β-arrestin recruitment, and for a synthetic biased agonist that only stimulates β-arrestin recruitment. The endogenous and β-arrestin–biased agonists induced two different ensembles of phosphorylation sites along the C-terminal tail. The phosphorylation of eight serine and threonine residues in the proximal and middle portions of the tail was required for full β-arrestin functionality, whereas phosphorylation of the serine and threonine residues in the distal portion of the tail had little influence on β-arrestin function. Similarly, molecular dynamics simulations showed that the proximal and middle clusters of phosphorylated residues were critical for stable β-arrestin–receptor interactions. These findings demonstrate that ligands that stabilize different receptor conformations induce different phosphorylation clusters in the C-terminal tail as barcodes to evoke distinct receptor-transducer engagement, receptor trafficking, and signaling. Editor's summary: The specific patterns of phosphorylation in the intracellular tail of a G protein–coupled receptor (GPCR) are thought to act as a barcode that determines whether G proteins are stimulated or β-arrestins are recruited. Gareri et al. investigated the role of phosphorylation barcodes in signaling by the angiotensin II type 1 receptor (AT1R). AT1R elicits both G protein activation and β-arrestin recruitment in response to the endogenous agonist AngII but stimulates only β-arrestin recruitment in response to a synthetic biased agonist. The authors identified patterns of serine and threonine phosphorylation that stabilized specific conformations of β-arrestin and were necessary for β-arrestin function. These findings demonstrate the importance of phosphorylation barcodes in determining the consequences of AT1R activation. —Annalisa M. VanHook [ABSTRACT FROM AUTHOR]
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- 2024
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31. The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9‐Mediated Splicing of NFATc4.
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Yu, Shuting, Sun, ZhiYong, Ju, Tiantian, Liu, Yingqi, Mei, Zhongting, Wang, Changhao, Qu, Zhezhe, Li, Na, Wu, Fan, Liu, KuiWu, Lu, Meixi, Huang, Min, Pang, Xiaochen, Jia, Yingqiong, Li, Ying, Zhang, Yaozhi, Dou, Shunkang, Jiang, Jianhao, Dong, Xianhui, and Huang, Chuanhao
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CARDIAC hypertrophy , *ALTERNATIVE RNA splicing , *ANGIOTENSIN II , *GENE expression , *HEART fibrosis - Abstract
Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Mesenchymal stromal cell-derived exosomes protect against abdominal aortic aneurysm formation through CD74 modulation of macrophage polarization in mice.
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Xu, Jiamin, Zhao, Jiling, Chen, Haiting, Tan, Xi, Zhang, Wenfeng, Xia, Zhongnan, Yao, Dejiang, Lei, Yuhua, Xu, Biao, Wei, Zhonghai, and Hu, Jiaxin
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ABDOMINAL aortic aneurysms , *TREATMENT effectiveness , *ANGIOTENSIN II , *TRANSMISSION electron microscopy , *STROMAL cells - Abstract
Background: Mesenchymal stromal cell (MSC)-derived exosomes (MSC-Exo) have been recognized for their significant role in regulating macrophage polarization, a process crucial to the pathogenesis of abdominal aortic aneurysm (AAA). However, the therapeutic effects of MSC-Exo on AAA remain largely unexplored. Therefore, this study aimed to investigate the functional and mechanistic aspects of MSC-Exo in the progression of AAA. Methods: The MSC-derived exosomes were characterized using Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Western blotting. An experimental mouse model of AAA was established through the administration of angiotensin II (Ang II) in male apoe−/− mice and calcium chloride (CaCl2) in male C57/B6 mice, with subsequent tail vein injection of exosomes to evaluate their efficacy against AAA. Macrophage polarization was assessed using immunofluorescence staining and WB analysis. Mechanistic analysis was performed using 4D Label-free Proteomics analysis. Results: We found that intravenous administration of MSC-Exo induced M2 polarization of macrophages within an inflammatory environment, effectively impeding AAA development in Ang II or CaCl2-induced AAA model. The therapeutic efficacy of MSC-Exo treatment was dependent on the presence of macrophages. Mechanistically, MSC-Exo suppressed the levels of cluster of differentiation 74 (CD74), modulating macrophage polarization through the TSC2-mTOR-AKT pathway. These findings highlight the potential of MSC-Exo as a therapeutic strategy for AAA by modulating macrophage polarization. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Effect of the combination of dexmedetomidine and sufentanil after laparoscopic cholecystectomy in patients with gallbladder diseases.
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Yan Chen, Xiangliu Liu, Gaohua Wang, and Haifeng Guo
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TUMOR necrosis factors , *ANGIOTENSIN II , *REACTIVE oxygen species , *VISUAL analog scale , *C-reactive protein , *SUFENTANIL - Abstract
Purpose: To investigate the effect of dexmedetomidine plus sufentanil on in-patients after laparoscopic cholecystectomy (LC). Methods: A total of 120 patients with gallbladder disease in Jingxian Hospital, China who were treated with LC were assigned equally to control and study cohorts. Control group received sufentanil, while study group received dexmedetomidine and sufentanil after surgery. The extent of sedation, degree of pain, and dosage of self-controlled analgesia pump drug, were evaluated within 48 h. Serum levels of stress indicators such as cortisol (Cor), norepinephrine (NE), angiotensin II (AngII), reactive oxygen species (ROS), and inflammatory factors: interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were determined. Results: Values of Ramsay sedation scores after surgery in study group were significantly higher than those in control group (p < 0.05). The visual analogue scale (VAS) scores were significantly lower in study group than in control group. The self-controlled analgesia pump drug dosages were significantly lower in study cohort (p < 0.05). Study cohort had lower levels of Cor, NE, AngII, TNF-α, and hs-CRP after surgery than control cohort, while SOD level was higher in study cohort than in control cohort (p < 0.05). There was a significantly lower incidence of adverse reactions in study cohort. Conclusion: The combination of dexmedetomidine and sufentanil as postoperative analgesia in LC significantly improves sedation and analgesia, reduces sufentanil use, alleviates stress response and inflammation, and reduces adverse reactions. Future long-term and large-scale monitoring is required to further validate these findings. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Angiotensin II Alters Mitochondrial Membrane Potential and Lipid Metabolism in Rat Colonic Epithelial Cells.
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Toth, Darby D., Souder II, Christopher L., Patuel, Sarah, English, Cole D., Konig, Isaac, Ivantsova, Emma, Malphurs, Wendi, Watkins, Jacqueline, Anne Costa, Kaylie, Bowden, John A., Zubcevic, Jasenka, and Martyniuk, Christopher J.
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PYRUVATE dehydrogenase kinase , *CELL metabolism , *LIPID metabolism , *MEMBRANE lipids , *BIOENERGETICS - Abstract
An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1–5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 (PDK2) was increased, and PDK2 can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Efficacy and Safety of Perioperative Angiotensin II Versus Phenylephrine as a First‐Line Continuous Infusion Vasopressor in Kidney Transplant Recipients.
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Beltran, Lyra P., Benken, Jamie, Jou, Jonathan, Benedetti, Enrico, Nishioka, Hokuto, Alamreia, Enas, Belcher, Rachel M., and Benken, Scott T.
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ANGIOTENSIN II , *KIDNEY transplantation , *VASOCONSTRICTORS , *PHENYLEPHRINE , *BLOOD pressure - Abstract
Introduction: Angiotensin II (ATII) maintains blood pressure via RAAS with a beneficial adverse effect profile versus catecholamines and phenylephrine. Head‐to‐head data comparing ATII to phenylephrine are lacking regarding renal allograft function, hemodynamic efficacy, and safety within the perioperative period of kidney transplantation. Methods: This single‐center, retrospective study included adult kidney transplant recipients who received continuous infusions of ATII or phenylephrine within a 24‐h perioperative period as a first‐line vasopressor according to an institutional algorithm. The primary endpoint was allograft function. Secondary endpoints were hemodynamic efficacy and adverse effects. Results: Among 105 patients, there was no significant difference in IGF (p = 0.545), SGF (p = 0.557), or DGF (p = 0.878) between patient cohorts. In the 34 patients with cold ischemia time (CIT) > 14‐h, IGF was higher (p = 0.013) and DGF (p = 0.045) was lower in the ATII cohort versus phenylephrine. In all patients, ATII was associated with a decreased need for additional vasopressor agents (p < 0.001). Adverse effect profiles were similar between cohorts (p > 0.05). Conclusion: Among kidney transplant recipients, ATII may be a suitable first‐line alternative compared with phenylephrine in the perioperative period for hypotension management with a reduced need for additional vasopressor support. Allograft benefits were observed in patients with prolonged CIT. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension.
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Bautista-Pérez, Rocio and Franco, Martha
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PURINERGIC receptors , *CHRONIC kidney failure , *ANGIOTENSIN II , *CARDIOLOGICAL manifestations of general diseases , *KIDNEY physiology - Abstract
The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Interaction between angiotensin-converting enzyme gene rs4343 polymorphism, environment factors, and angiotensin II level on susceptibility to knee osteoarthritis.
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Elnaggar, Basma Mohammed Mohammed Ali, Abd Elbaky, Nashwa Mohamed, Albeltagy, Eman Salah, and El Zomor, Hala Mohamed
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ANGIOTENSIN II , *GENETIC polymorphisms , *KNEE osteoarthritis , *ANGIOTENSIN converting enzyme , *HEREDITY - Abstract
Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level. Using a case–control design, we recruited 200 subjects (100 cases and 100 controls) and all were subjected to genotyping of rs4343 SNP by real-time polymerase chain reaction and assay of serum angiotensin II level by ELISA. G containing genotypes (AG and GG) and G allele frequencies of the ACE rs4343 polymorphism were significantly higher in the case group than that in the control group. There was significant association between ACE rs4343 genotypes and risk of knee OA under the following genetic inheritance models: GG vs. AA (P = 0.003), AA vs. GG/AG (P = 0.014), AG/AA vs. GG (P = 0.037), and G vs. A (P < 0.001). Stratified analyses showed ACE rs4343 polymorphism was evidently associated with a significantly increased risk of knee OA among those had BMI ≥ 25% (adjusted OR = 3.016; 95% CI 1.052–8.648; P = 0.040). Additionally, knee OA patients with GG genotype had greater knee specific WOMAC index, Kellgren score, and serum angiotensin II level than those with AA or GA genotypes. The investigated polymorphism in the ACE gene rs4343 may reflect the risk and severity of knee OA in the Egyptian population, particularly with the GG genotype. The interaction between ACE gene rs4343 polymorphism and obesity further increased the risk of knee OA. Moreover, the higher angiotensin II level may be involved in the pathogenesis of knee OA. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Elevated Salt or Angiotensin II Levels Induce CD38+ Innate Immune Cells in the Presence of Granulocyte-Macrophage Colony Stimulating Factor.
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Smith, Hannah L., Goodlett, Bethany L., Navaneethabalakrishnan, Shobana, and Mitchell, Brett M.
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CD38 antigen , *ANGIOTENSIN II , *DENDRITIC cells , *BLOOD pressure , *IMMUNE system - Abstract
Hypertension (HTN) impacts almost half of adults, predisposing them to cardiovascular disease and renal damage. Salt-sensitive HTN (SSHTN) and angiotensin II (A2)-induced HTN (A2HTN) both involve immune system activation and renal innate immune cell infiltration. Subpopulations of activated [Cluster of differentiation 38 (CD38)] innate immune cells, such as macrophages and dendritic cells (DCs), play distinct roles in modulating renal function and blood pressure. It is unknown how these cells become CD38+ or which subtypes are pro-hypertensive. When bone marrow-derived monocytes (BMDMs) were grown in granulocyte-macrophage colony stimulating factor (GM-CSF) and treated with salt or A2, CD38+ macrophages and CD38+ DCs increased. The adoptive transfer of GM-CSF-primed BMDMs into mice with either SSHTN or A2HTN increased renal CD38+ macrophages and CD38+ DCs. Flow cytometry revealed increased renal M1 macrophages and type-2 conventional DCs (cDC2s), along with their CD38+ counterparts, in mice with either SSHTN or A2HTN. These results were replicable in vitro. Either salt or A2 treatment of GM-CSF-primed BMDMs significantly increased bone marrow-derived (BMD)-M1 macrophages, CD38+ BMD-M1 macrophages, BMD-cDC2s, and CD38+ BMD-cDC2s. Overall, these data suggest that GM-CSF is necessary for the salt or A2 induction of CD38+ innate immune cells, and that CD38 distinguishes pro-hypertensive immune cells. Further investigation of CD38+ M1 macrophages and CD38+ cDC2s could provide new therapeutic targets for both SSHTN and A2HTN. [ABSTRACT FROM AUTHOR]
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- 2024
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39. High Dose of Estrogen Protects the Lungs from Ischemia–Reperfusion Injury by Downregulating the Angiotensin II Signaling Pathway.
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Dai, Peng, He, Jutong, Wei, Yanhong, Xu, Ming, Zhao, Jinping, Zhou, Xuefeng, and Tang, Hexiao
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ANGIOTENSIN-receptor blockers , *ANGIOTENSIN II , *FULVESTRANT , *TRANSMISSION electron microscopy , *EPITHELIAL cells , *REPERFUSION injury , *LOSARTAN - Abstract
We explored the sex difference in lung ischemia–reperfusion injury (LIRI) and the role and mechanism of estrogen (E2) and angiotensin II (Ang II) in LIRI. We established a model of LIRI in mice. E2, Ang II, E2 inhibitor (fulvestrant), and angiotensin II receptor blocker (losartan) were grouped for treatment. The lung wet/dry weight ratio, natural killer (NK) cells (by flow cytometry), neutrophils (by flow cytometry), expression of key proteins (by Western blot, immunohistochemistry, ELISA, and immunofluorescence), and expression of related protein mRNA (by qPCR) were detected. The ultrastructure of the alveolar epithelial cells was observed by transmission electron microscopy. We found that E2 and Ang II played an important role in the progression of LIRI. The two signaling pathways showed obvious antagonism, and E2 regulates LIRI in the different sexes by downregulating Ang II, leading to a better prognosis. E2 and losartan reduced the inflammatory cell infiltration in lung tissue and key inflammatory factors in serum while fulvestrant and Ang II had the opposite effect. The protective effect of E2 was related with AKT, p38, COX2, and HIF-1α. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Androgen aggravates aortic aneurysms via suppression of PD-1 in mice.
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Xufang Mu, Shu Liu, Zhuoran Wang, Kai Jiang, McClintock, Tim, Stromberg, Arnold J., Lee, Eugene S., Curci, John A., Gong, Ming C., and Zhenheng Guo
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AORTIC aneurysms , *PROGRAMMED cell death 1 receptors , *IMMUNE checkpoint proteins , *ANDROGENS , *ANGIOTENSIN II - Abstract
Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms (AAs), a devastating vascular disease with a higher prevalence and fatality rate in men than in women. However, the mechanism by which androgen mediates AAs is largely unknown. Here, we found that male, not female, mice developed AAs when exposed to aldosterone and high salt (Aldo-salt). We revealed that androgen and androgen receptors (ARs) were crucial for this sexually dimorphic response to Aldo-salt. We identified programmed cell death protein 1 (PD-1), an immune checkpoint, as a key link between androgen and AAs. Furthermore, we demonstrated that administration of anti--PD-1 Ab and adoptive PD-1--deficient T cell transfer reinstated Aldo-salt--induced AAs in orchiectomized mice and that genetic deletion of PD-1 exacerbated AAs induced by a high-fat diet and angiotensin II (Ang II) in nonorchiectomized mice. Mechanistically, we discovered that the AR bound to the PD-1 promoter to suppress the expression of PD-1 in the spleen. Thus, our study unveils a mechanism by which androgen aggravates AAs by suppressing PD-1 expression in T cells. Moreover, our study suggests that some patients with cancer might benefit from screenings for AAs during immune checkpoint therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Vasopressor Responsiveness 101: Prediction of Responsiveness to Angiotensin II Infusion.
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Russell, James A.
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ANGIOTENSIN-receptor blockers , *ANGIOTENSIN II , *MYOCARDIAL infarction , *ANGIOTENSIN I , *COVID-19 , *COMMUNITY-acquired pneumonia - Abstract
The article discusses a study on the association between renin levels and angiotensin II infusion dose in patients with vasopressor-dependent hypotension. The study found that baseline renin levels were predictive biomarkers for response to angiotensin II infusion and that patients with high renin levels required a higher dose of angiotensin II. The study also highlighted the potential cardiac safety of angiotensin II infusion in cardiac surgery patients. However, the study has limitations and further research is needed to confirm the findings. The text emphasizes the importance of personalized physiologic management strategies in traumatic brain injury treatment. [Extracted from the article]
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- 2024
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42. Renin Levels and Angiotensin II Responsiveness in Vasopressor-Dependent Hypotension.
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See, Emily J., Chaba, Anis, Spano, Sofia, Maeda, Akinori, Clapham, Caroline, Burrell, Louise M., Liu, Jasmine, Khasin, Monique, Liskaser, Grace, Eastwood, Glenn, and Bellomo, Rinaldo
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ANGIOTENSIN II , *RENIN , *HYPOTENSION , *RENAL replacement therapy , *RENIN-angiotensin system - Abstract
OBJECTIVES: The relationship between renin levels, exposure to renin-angiotensin system (RAS) inhibitors, angiotensin II (ANGII) responsiveness, and outcome in patients with vasopressor-dependent vasodilatory hypotension is unknown. DESIGN: We conducted a single-center prospective observational study to explore whether recent RAS inhibitor exposure affected baseline renin levels, whether baseline renin levels predicted ANGII responsiveness, and whether renin levels at 24 hours were associated with clinical outcomes. SETTING: An academic ICU in Melbourne, VIC, Australia. PATIENTS: Forty critically ill adults who received ANGII as the primary agent for vasopressor-dependent vasodilatory hypotension who were included in the Acute Renal effects of Angiotensin II Management in Shock study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After multivariable adjustment, recent exposure to a RAS inhibitor was independently associated with a relative increase in baseline renin levels by 198% (95% CI, 36-552%). The peak amount of ANGII required to achieve target mean arterial pressure was independently associated with baseline renin level (increase by 46% per ten-fold increase; 95% CI, 8--98%). Higher renin levels at 24 hours after ANGII initiation were independently associated with fewer days alive and free of continuous renal replacement therapy (CRRT) (-7 d per ten-fold increase; 95% CI, -12 to -1). CONCLUSIONS: In patients with vasopressor-dependent vasodilatory hypotension, recent RAS inhibitor exposure was associated with higher baseline renin levels. Such higher renin levels were then associated with decreased ANGII responsiveness. Higher renin levels at 24 hours despite ANGII infusion were associated with fewer days alive and CRRT-free. These preliminary findings emphasize the importance of the RAS and the role of renin as a biomarker in patients with vasopressor-dependent vasodilatory hypotension. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Deacetylation mimetic mutation of mitochondrial SOD2 attenuates ANG II-induced hypertension by protecting against oxidative stress and inflammation.
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Dikalova, Anna, Ao, Mingfang, Tkachuk, Liliya, and Dikalov, Sergey
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OXIDATIVE stress , *HYPERTENSION , *BLOOD pressure , *MITOCHONDRIA , *ANGIOTENSIN II , *DEACETYLATION , *ESSENTIAL hypertension - Abstract
Almost one-half of adults have hypertension, and blood pressure is poorly controlled in a third of patients despite the use of multiple drugs, likely because of mechanisms that are not affected by current treatments. Hypertension is linked to oxidative stress; however, common antioxidants are ineffective. Hypertension is associated with inactivation of key intrinsic mitochondrial antioxidant, superoxide dismutase 2 (SOD2), due to hyperacetylation, but the role of specific SOD2 lysine residues has not been defined. Hypertension is associated with SOD2 acetylation at lysine 68, and we suggested that deacetylation mimetic mutation of K68 to arginine in SOD2 inhibits vascular oxidative stress and attenuates hypertension. To test this hypothesis, we have developed a new deacetylation mimetic SOD2-K68R mice. We performed in vivo studies in SOD2-K68R mice using angiotensin II (ANG II) model of vascular dysfunction and hypertension. ANG II infusion in wild-type mice induced vascular inflammation and oxidative stress and increased blood pressure to 160 mmHg. SOD2-K68R mutation completely prevented increase in mitochondrial superoxide, abrogated vascular oxidative stress, preserved endothelial nitric oxide production, protected vasorelaxation, and attenuated ANG II-induced hypertension. ANG II and cytokines contribute to vascular oxidative stress and hypertension. Treatment of wild-type aortas with ANG II and cytokines in organoid culture increased mitochondrial superoxide twofold, which was completely prevented in aortas isolated from SOD2-K68R mice. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and pathogenesis of hypertension. We conclude that strategies to reduce SOD2 acetylation may have therapeutic potential in the treatment of vascular dysfunction and hypertension. NEW & NOTEWORTHY: Essential hypertension is associated with hyperacetylation of key mitochondrial antioxidant SOD2; however, the pathophysiological role of SOD2 acetylation has not been defined. Our animal study of angiotensin II hypertension model shows that deacetylation mimetic SOD2-K68R mutation prevents pathogenic increase in vascular mitochondrial superoxide, abrogates vascular oxidative stress, preserves endothelial nitric oxide, protects endothelial-dependent vasorelaxation, and attenuates hypertension. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and the pathogenesis of hypertension. [ABSTRACT FROM AUTHOR]
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- 2024
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44. The role of β‐adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do β‐adrenergic receptor agonists and antagonists protect the heart?
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Maslov, Leonid N., Naryzhnaya, Natalia V., Voronkov, Nikita S., Kurbatov, Boris K., Derkachev, Ivan A., Ryabov, Vyacheslav V., Vyshlov, Evgeny V., Kolpakov, Viktor V., Tomilova, Eugenia A., Sapozhenkova, Ekaterina V., Singh, Nirmal, Fu, Feng, and Pei, Jianming
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HEART , *REPERFUSION , *MYOCARDIAL infarction , *CORONARY occlusion , *ISCHEMIA , *CORONARY artery bypass , *ANGIOTENSIN II , *GABA receptors - Abstract
Background: Catecholamines and β‐adrenergic receptors (β‐ARs) play an important role in the regulation of cardiac tolerance to the impact of ischemia and reperfusion. This systematic review analyzed the molecular mechanisms of the cardioprotective activity of β‐AR ligands. Methods: We performed an electronic search of topical articles using PubMed databases from 1966 to 2023. We cited original in vitro and in vivo studies and review articles that documented the cardioprotective properties of β‐AR agonists and antagonists. Results: The infarct‐reducing effect of β‐AR antagonists did not depend on a decrease in the heart rate. The target for β‐blockers is not only cardiomyocytes but also neutrophils. β1‐blockers (metoprolol, propranolol, timolol) and the selective β2‐AR agonist arformoterol have an infarct‐reducing effect in coronary artery occlusion (CAO) in animals. Antagonists of β1‐ and β2‐АR (metoprolol, propranolol, nadolol, carvedilol, bisoprolol, esmolol) are able to prevent reperfusion cardiac injury. All β‐AR ligands that reduced infarct size are the selective or nonselective β1‐blockers. It was hypothesized that β1‐AR blocking promotes an increase in cardiac tolerance to I/R. The activation of β1‐AR, β2‐AR, and β3‐AR can increase cardiac tolerance to I/R. The cardioprotective effect of β‐AR agonists is mediated via the activation of kinases and reactive oxygen species production. Conclusions: It is unclear why β‐blockers with the similar receptor selectivity have the infarct‐sparing effect while other β‐blockers with the same selectivity do not affect infarct size. What is the molecular mechanism of the infarct‐reducing effect of β‐blockers in reperfusion? Why did in early studies β‐blockers decrease the mortality rate in patients with acute myocardial infarction (AMI) and without reperfusion and in more recent studies β‐blockers had no effect on the mortality rate in patients with AMI and reperfusion? The creation of more effective β‐AR ligands depends on the answers to these questions. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Angiotensin-(1-12): Does It Exist? A Critical Evaluation in Humans, Rats, and Mice.
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Rodrigues, André F., Domenig, Oliver, Poglitsch, Marko, Bader, Michael, and Jan Danser, A. H.
- Abstract
BACKGROUND: Angiotensin-(1-12), measured by a self-developed, polyclonal antibody-based radioimmunoassay, has been suggested to act as an alternative precursor of angiotensin II. A more reliable detection method would be liquid chromatography-tandem mass spectrometry. METHODS: We set up the quantification of human and murine angiotensin-(1-12) by liquid chromatography-tandem mass spectrometry and then used this method to measure angiotensin-(1-12) in human, rat, and mouse blood samples, as well as in mouse brain, mouse kidney, and rat heart. We also verified ex vivo angiotensin-(1-12) generation and metabolism in human blood samples incubated at 37 °C. RESULTS: Stabilization of blood in guanidine hydrochloride was chosen for sample collection since this allowed full recovery of spiked angiotensin-(1-12). Angiotensin-(1-12) was undetectable in human blood samples when incubating nonstabilized plasma at 37 °C, while angiotensin-(1-12) added to nonstabilized human plasma disappeared within 10 minutes. Stabilized human blood samples contained angiotensin II, while angiotensin-(1-12) was undetectable. Blood, hearts, and kidneys, but not brains, of wild-type mice and rats contained detectable levels of angiotensin II, while angiotensin-(1-12) was undetectable. In renin knockout mice, all angiotensins, including angiotensin-(1-12), were undetectable at all sites, despite a 50% rise in angiotensinogen. Angiotensin-(1-12) metabolism in human blood plasma was not affected by renin inhibition. Yet, blockade of angiotensin-converting enzyme and aminopeptidase A, but not of chymase, neutral endopeptidase, or prolyl oligopeptidase, prolonged the half-life of angiotensin-(1-12), and angiotensin-converting enzyme inhibition prevented the formation of angiotensin II. CONCLUSIONS: We were unable to detect intact angiotensin-(1-12) in humans, rats, and mice, either in blood or tissue, suggesting that this metabolite is an unlikely source of endogenous angiotensins. [ABSTRACT FROM AUTHOR]
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- 2024
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46. CTRP3/AMPK pathway plays a key role in the anti-hypertrophic effects of cyanidin-3-O-glucoside by inhibiting the inflammatory response.
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Xueli Zhang and Xiaoyi Qin
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CARDIAC hypertrophy ,HEART fibrosis ,AMP-activated protein kinases ,INFLAMMATION ,SYMPTOMS ,ANGIOTENSIN II - Abstract
Background. Cardiac hypertrophy can be a pathological process that impairs heart function. Anthocyanins are a well-characterized type of natural antioxidant, and recent studies have shown that this type of compound has potential cardioprotective effects against different disorders, such as cardiac hypertrophy. Objectives. We assessed the anti-hypertrophy potential of cyanidin-3-O-glucoside (C3G) and the mechanism associated with any observed effects. Materials and methods. Hypertrophy symptoms were induced using the transverse aortic constriction (TAC) operation in vivo and angiotensin II (Ang II) in vitro. The effect of C3G on the development of hypertrophic symptoms was then determined. Moreover, we examined the influence of CTRP3 inhibition on the anti-hypertrophy function of C3G. Results. The TAC operation induced cardiac fibrosis and heart weight increase, which was associated with increased production of cytokines and suppressed activity of the CTRP3/AMPK pathway. The impairments of heart structure and function were attenuated by C3G. Angiotensin II induced size increases of neonatal rat cardiomyocytes (NRCMs) in vitro, and this effect was inhibited by C3G. Furthermore, the inhibition of CTRP3 counteracted the function of C3G by promoting NRCM hyperplasia and inflammation. Conclusions. The results of the current study showed that the activation of CTRP3 contributed to the antihypertrophy effects of C3G. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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47. Angiotensin II as a Vasopressor for Perioperative Hypotension in Solid Organ Transplant.
- Author
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Benken, Scott T., Thomas, Riya, Fraidenburg, Dustin R., and Benken, Jamie J.
- Subjects
RENIN-angiotensin system ,LUNG transplantation ,TRANSPLANTATION of organs, tissues, etc. ,HEART transplantation ,LIVER transplantation - Abstract
During the perioperative period of transplantation, patients experience hypotension secondary to the side effects of anesthesia, surgical stress, inflammatory triggering, and intraoperative fluid shifts, among others causes. Vasopressor support, in this context, must reverse systemic hypotension, but ideally, the agents used should benefit allograft function and avoid the adverse events commonly seen after transplantation. Traditional therapies to reverse hypotension include catecholamine vasopressors (norepinephrine, epinephrine, dopamine, and phenylephrine), but their utility is limited when considering allograft complications and adverse events such as arrhythmias with agents with beta-adrenergic properties. Synthetic angiotensin II (AT2S–[Giapreza]) is a novel vasopressor indicated for distributive shock with a unique mechanism of action as an angiotensin receptor agonist restoring balance to an often-disrupted renin angiotensin aldosterone system. Additionally, AT2S provides a balanced afferent and efferent arteriole vasoconstriction at the level of the kidney and could avoid the arrhythmic complications of a beta-adrenergic agonist. While the data, to date, are limited, AT2S has demonstrated safety in case reports, pilot studies, and small series in the kidney, liver, heart, and lung transplant populations. There are physiologic and hemodynamic reasons why AT2S could be a more utilized agent in these populations, but further investigation is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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48. β-Adrenoceptor Agonists Attenuate Thrombin-Induced Impairment of Human Lung Endothelial Cell Barrier Function and Protect the Lung Vascular Barrier during Resuscitation from Hemorrhagic Shock.
- Author
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McGee, Michelle Y., Ogunsina, Ololade, Boshra, Sadia N., Gao, Xianlong, and Majetschak, Matthias
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VASOPRESSIN ,HEMORRHAGIC shock ,ANGIOTENSIN II ,BLOOD pressure ,VASOCONSTRICTORS - Abstract
β-adrenoceptor (β-AR) agonists are known to antagonize thrombin-induced impairment (TII) of bovine and ovine lung endothelial barrier function. The effects of adrenoceptor agonists and other vasoactive agents on human lung microvascular endothelial cell (HULEC-5a) barrier function upon thrombin exposure have not been studied. Furthermore, it is unknown whether the in vitro effects of adrenoceptor agonists translate to lung protective effects in vivo. We observed that epinephrine, norepinephrine, and phenylephrine enhanced normal and prevented TII of HULEC-5a barrier function. Arginine vasopressin and angiotensin II were ineffective. α
1B -, α2A/B -, and β1/2 -ARs were detectable in HULEC-5a by RT-PCR. Propranolol but not doxazosin blocked the effects of all adrenoceptor agonists. Phenylephrine stimulated β2 -AR-mediated Gαs activation with 13-fold lower potency than epinephrine. The EC50 to inhibit TII of HULEC-5a barrier function was 1.8 ± 1.9 nM for epinephrine and >100 nM for phenylephrine. After hemorrhagic shock and fluid resuscitation in rats, Evans blue extravasation into the lung increased threefold (p < 0.01 vs. sham). Single low-dose (1.8 μg/kg) epinephrine administration at the beginning of resuscitation had no effects on blood pressure and reduced Evans blue extravasation by 60% (p < 0.05 vs. vehicle). Our findings confirm the effects of β-adrenoceptor agonists in HULEC-5a and suggest that low-dose β-adrenoceptor agonist treatment protects lung vascular barrier function after traumatic hemorrhagic shock. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
49. Molecular changes in endometrium origin stromal cells during initiation of cardiomyogenic differentiation induced with Decitabine, Angiotensin II and TGF- β1.
- Author
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Skliutė, Giedrė, Staponkutė, Giedrė, Skliutas, Edvinas, Malinauskas, Mangirdas, and Navakauskienė, Rūta
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- *
STROMAL cells , *ENDOMETRIUM , *ANGIOTENSIN II , *TRANSCRIPTION factors , *GENETIC profile , *DECITABINE - Abstract
Stem cells' differentiation toward cardiac lineage is a complex process dependent on various alterations in molecular basis and regulation pathways. The aim of the study is to show that endometrium-derived stromal cells – menstrual, endometrial and endometriotic, could be an attractive source for examination of the mechanisms underlying cardiomyogenesis. After treatment with Decitabine, Angiotensin II and TGF-β1, cells demonstrated morphological dedifferentiation into early cardiomyocyte-like cells and expressed CD36, CD106, CD172a typically used to sort for human pluripotent stem cell-derived cardiomyocytes. RT-qPCR revealed changed cells' genetic profiles, as majority of cardiac lineage differentiation related genes and cardiac ion channels (calcium, sodium, potassium) coding genes were upregulated after 6 and 13 days of exposure. Additionally, analysis of expression of various signaling proteins (FOXO1, PDGFB, TGFBR1, mTOR, VEGFA, WNT4, Notch1) coding genes showed differences between cell cultures as they seem to employ distinct signaling pathways through differentiation initiation. Early stages of differentiation had biggest impact on cardiomyogenesis related proteins (Nkx-2.5, EZH2, FOXO3a, H3K9Ac) levels, as we noticed after conducting Western blot and as expected, early cardiac transcription factor Nkx-2.5 was highly expressed and localized in nucleus of differentiating cells. These findings led us to assess endometrium origin stromal cells' potential to differentiate towards cardiomyogenic lineage and better understand the regulation of complex differentiation processes in ex vivo model systems. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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50. Intra- and postoperative relative angiotensin II deficiency in patients undergoing elective major abdominal surgery.
- Author
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Krenn, Katharina, Höbart, Petra, Adam, Lukas, Riemann, Gregor, Christiansen, Finn, Domenig, Oliver, and Ullrich, Roman
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ABDOMINAL surgery ,REGULATION of blood pressure ,BLOOD proteins ,ANGIOTENSIN II ,ANGIOTENSIN converting enzyme - Abstract
Introduction: The classical axis of the renin--angiotensin system (RAS) makes an important contribution to blood pressure regulation under general anesthesia via the vasopressor angiotensin II (Ang II). As part of the alternative RAS, angiotensin-converting enzyme 2 (ACE2) modulates the pro-inflammatory and fibrotic effects of Ang II by processing it into the organ-protective Ang 1-7, which is cleaved to Ang 1-5 by ACE. Although the levels of ACE2 may be associated with postoperative complications, alternative RAS metabolites have never been studied perioperatively. This study was designed to investigate the perioperative kinetics and balance of both RAS axes around major abdominal surgery. Methods: In this observational cohort study, 35 patients undergoing elective major abdominal surgery were included. Blood sampling was performed before and after induction of anesthesia, at 1 h after skin incision, at the end of surgery, and on postoperative days (POD) 1, 3, and 7. The equilibrium concentrations of Ang I-IV, Ang 1-7, and Ang 1-5 in plasma were quantified using mass spectrometry. The plasma protein levels of ACE and ACE2 were measured with ELISA. Results: Surgery caused a rapid, transient, and primarily renin-dependent activation of both RAS axes that returned to baseline on POD 1, followed by suppression. After induction, the Ang II/Ang I ratio persistently decreased, while the ACE levels started to increase on POD 1 (all p < 0.01 versus before anesthesia). Conversely, the ACE2 levels increased on POD 3 and 7 (both p < 0.001 versus before anesthesia), when the median Ang 1-7 concentrations were unquantifiably low. Discussion: The postoperative elevation of ACE2 may prolong the decrease of the Ang II/Ang I ratio through the increased processing of Ang II. Further clarification of the intraoperative factors leading to relative Ang II deficiency and the sources of postoperatively elevated ACE2 is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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