Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury
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 CS...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.017544 |
| _version_ | 1811333965132333056 |
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| author | Huijing Xia Zhen Li Thomas E. Sharp David J. Polhemus Jean Carnal Karl H. Moles Ya‐Xiong Tao John Elrod Josef Pfeilschifter Karl‐Friedrich Beck David J. Lefer |
| author_facet | Huijing Xia Zhen Li Thomas E. Sharp David J. Polhemus Jean Carnal Karl H. Moles Ya‐Xiong Tao John Elrod Josef Pfeilschifter Karl‐Friedrich Beck David J. Lefer |
| author_sort | Huijing Xia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:00:56Z |
| format | Article |
| id | doaj.art-c13eff3d2bb24ff8b38bcf1072bbc657 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T17:00:56Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c13eff3d2bb24ff8b38bcf1072bbc6572022-12-22T02:38:39ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-10-0191910.1161/JAHA.120.017544Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion InjuryHuijing Xia0Zhen Li1Thomas E. Sharp2David J. Polhemus3Jean Carnal4Karl H. Moles5Ya‐Xiong Tao6John Elrod7Josef Pfeilschifter8Karl‐Friedrich Beck9David J. Lefer10Cardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LACardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LACardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LACardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LACardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LACardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LADepartment of Anatomy, Physiology, and Pharmacology College of Veterinary Medicine Auburn University Auburn ALCenter for Translational Medicine Lewis Katz School of Medicine Temple University Philadelphia PAInstitute of Pharmacology and Toxicology Goethe University Frankfurt am Main GermanyInstitute of Pharmacology and Toxicology Goethe University Frankfurt am Main GermanyCardiovascular Center of Excellence Louisiana State University Health Sciences Center New Orleans LABackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.120.017544cardioprotectioncystathionine γ‐lyaseendothelial functionhydrogen sulfidenitric oxide |
| spellingShingle | Huijing Xia Zhen Li Thomas E. Sharp David J. Polhemus Jean Carnal Karl H. Moles Ya‐Xiong Tao John Elrod Josef Pfeilschifter Karl‐Friedrich Beck David J. Lefer 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 cardioprotection cystathionine γ‐lyase endothelial function hydrogen sulfide nitric oxide |
| title | Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury |
| title_full | Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury |
| title_fullStr | Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury |
| title_full_unstemmed | Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury |
| title_short | Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury |
| title_sort | endothelial cell cystathionine γ lyase expression level modulates exercise capacity vascular function and myocardial ischemia reperfusion injury |
| topic | cardioprotection cystathionine γ‐lyase endothelial function hydrogen sulfide nitric oxide |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.017544 |
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