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Endothelial Cell Cystathionine γ-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury.
J Am Heart Assoc. 2020 10 20; 9(19):e017544.JA

Abstract

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32990120

Citation

Xia, Huijing, et al. "Endothelial Cell Cystathionine γ-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury." Journal of the American Heart Association, vol. 9, no. 19, 2020, pp. e017544.
Xia H, Li Z, Sharp TE, et al. Endothelial Cell Cystathionine γ-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury. J Am Heart Assoc. 2020;9(19):e017544.
Xia, H., Li, Z., Sharp, T. E., Polhemus, D. J., Carnal, J., Moles, K. H., Tao, Y. X., Elrod, J., Pfeilschifter, J., Beck, K. F., & Lefer, D. J. (2020). Endothelial Cell Cystathionine γ-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury. Journal of the American Heart Association, 9(19), e017544. https://doi.org/10.1161/JAHA.120.017544
Xia H, et al. Endothelial Cell Cystathionine γ-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury. J Am Heart Assoc. 2020 10 20;9(19):e017544. PubMed PMID: 32990120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelial Cell Cystathionine γ-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury. AU - Xia,Huijing, AU - Li,Zhen, AU - Sharp,Thomas E,3rd AU - Polhemus,David J, AU - Carnal,Jean, AU - Moles,Karl H, AU - Tao,Ya-Xiong, AU - Elrod,John, AU - Pfeilschifter,Josef, AU - Beck,Karl-Friedrich, AU - Lefer,David J, Y1 - 2020/09/29/ PY - 2020/9/30/pubmed PY - 2021/3/16/medline PY - 2020/9/29/entrez KW - cardioprotection KW - cystathionine γ‐lyase KW - endothelial function KW - hydrogen sulfide KW - nitric oxide SP - e017544 EP - e017544 JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 9 IS - 19 N2 - 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. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/32990120/Endothelial_Cell_Cystathionine_γ_Lyase_Expression_Level_Modulates_Exercise_Capacity_Vascular_Function_and_Myocardial_Ischemia_Reperfusion_Injury_ L2 - https://www.ahajournals.org/doi/10.1161/JAHA.120.017544?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -