Abstract 13455: Endothelium-Derived Hydrogen Sulfide Modulates Endothelial-Mesenchymal Transition in Heart Failure
| Autor: | Zhen Li, Huijing Xia, Thomas E Sharp, Kyle Lapenna, John W Elrod, Josef Pfeilschifter, Karl-Friedrich Beck, Traci T Goodchild, David J Lefer |
|---|---|
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Circulation. 144 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.144.suppl_1.13455 |
| Popis: | Introduction: Hydrogen sulfide (H 2 S) is a critical endogenous signaling molecule that exerts protective effects in the setting of heart failure (HF). Cystathionine γ-lyase (CSE), one of three H 2 S producing enzyme, is predominantly localized in the vascular endothelium. The interaction between endothelial cell derived H 2 S and endothelial-mesenchymal transition (EndoMT), an important pathological process contributing to the formation of fibrosis, has yet to be investigated. Methods: Endothelial cell specific CSE knockout (EC-CSE KO) and overexpressing (EC-CSE Tg) mice were subjected to transverse aortic constriction (TAC) to induce HF with reduced ejection fraction (HFrEF). Cardiac function, vascular reactivity, and treadmill exercise capacity following TAC were measured to determine the severity of HF. Histological analysis was performed to investigate changes in cardiac fibrosis. Vimentin and Von Willebrand factor co-immunostaining were utilized to investigate EndoMT activation. Results: EC-CSE KO mice exhibited reduced circulating H 2 S level, which was accompanied by increased EndoMT in the myocardium, resulting in increased perivascular fibrosis in the heart, impaired cardiac and vascular function, and worsened exercise performance. In contrast, genetic overexpression of CSE in endothelial cells elevated circulating and myocardial H 2 S, led to decreased EndoMT and subsequent fibrosis, preserved cardiac and endothelial function, and improved exercise capacity. Conclusions: Our data demonstrate that endothelial CSE modulates endothelial-mesenchymal transition to ameliorate the severity of pressure overload - induced heart failure. These data further suggest that endothelium-derived H 2 S is a potential therapeutic for the treatment of heart failure with reduced ejection fraction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|