Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Jean Carnal¹  Thomas E. Sharp¹  David J. Lefer¹  David J. Polhemus¹  Huijing Xia¹  Karl H. Moles¹  Zhen Li¹  John Elrod²  Ya‐Xiong Tao³  Josef Pfeilschifter⁴  Karl‐Friedrich Beck⁴ 

[1] Cardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LA;Center for Translational Medicine Lewis Katz School of Medicine Temple University Philadelphia PA;Department of Anatomy, Physiology, and Pharmacology College of Veterinary Medicine Auburn University Auburn AL;Institute of Pharmacology and Toxicology Goethe University Frankfurt am Main Germany;

关键词: cardioprotection;    cystathionine γ‐lyase;    endothelial function;    hydrogen sulfide;    nitric oxide;   

DOI  :  10.1161/JAHA.120.017544

来源: DOAJ

【 摘 要 】

Background Hydrogen sulfide (H2S) is an important endogenous physiological signaling molecule and exerts protective properties in the cardiovascular system. Cystathionine γ‐lyase (CSE), 1 of 3 H2S producing enzyme, is predominantly localized in the vascular endothelium. However, the regulation of CSE in vascular endothelium remains incompletely understood. Methods and Results We generated inducible endothelial cell‐specific CSE overexpressed transgenic mice (EC‐CSE Tg) and endothelial cell‐specific CSE knockout mice (EC‐CSE KO), and investigated vascular function in isolated thoracic aorta, treadmill exercise capacity, and myocardial injury following ischemia‐reperfusion in these mice. Overexpression of CSE in endothelial cells resulted in increased circulating and myocardial H2S and NO, augmented endothelial‐dependent vasorelaxation response in thoracic aorta, improved exercise capacity, and reduced myocardial‐reperfusion injury. In contrast, genetic deletion of CSE in endothelial cells led to decreased circulating H2S and cardiac NO production, impaired endothelial dependent vasorelaxation response and reduced exercise capacity. However, myocardial‐reperfusion injury was not affected by genetic deletion of endothelial cell CSE. Conclusions CSE‐derived H2S production in endothelial cells is critical in maintaining endothelial function, exercise capacity, and protecting against myocardial ischemia/reperfusion injury. Our data suggest that the endothelial NO synthase—NO pathway is likely involved in the beneficial effects of overexpression of CSE in the endothelium.

【 授权许可】

Unknown