Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Relief of Pressure Overload in Mice
Autor: | Xueling Li, Lihong Wang, Yaru Zheng, Qinggang Zhang, Qin Zhu, Qingcheng Wang, Qinyang Jin |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Angiotensin receptor Inflammasomes Cardiac fibrosis Tetrazoles 030204 cardiovascular system & hematology Ventricular Function Left Sacubitril 0302 clinical medicine Pharmacology (medical) Ventricular Remodeling Aminobutyrates NF-kappa B General Medicine Drug Combinations Valsartan Cardiology Hypertrophy Left Ventricular Neprilysin Original Article Cardiology and Cardiovascular Medicine Signal Transduction medicine.drug Cardiac function curve medicine.medical_specialty 03 medical and health sciences Internal medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Protease Inhibitors Sacubitril/valsartan Cardiac remodeling Pharmacology Pressure overload business.industry Myocardium Pressure unloading Biphenyl Compounds medicine.disease Fibrosis NLRP3 inflammasome Mice Inbred C57BL Disease Models Animal 030104 developmental biology Heart failure business Angiotensin II Type 1 Receptor Blockers Sacubitril Valsartan |
Zdroj: | Cardiovascular Drugs and Therapy |
ISSN: | 1573-7241 0920-3206 |
Popis: | Background/aims The persistent existence of pathological cardiac remodeling, resulting from aortic stenosis, is related to poor clinical prognosis after successful transcatheter aortic valve replacement (TAVR). Sacubitril/valsartan (Sac/Val), comprising an angiotensin receptor blocker and a neprilysin inhibitor, has been demonstrated to have a beneficial effect against pathological cardiac remodeling, including cardiac fibrosis and inflammation in heart failure. The aim of this study was to determine whether Sac/Val exerts a cardioprotective effect after pressure unloading in mice. Methods and results Male C57BL/6 J mice were subjected to debanding (DB) surgery after 8 weeks (wk) of aortic banding (AB). Cardiac function was assessed by echocardiography, which indicated a protective effect of Sac/Val after DB. After treatment with Sac/Val post DB, decreased heart weight and myocardial cell size were observed in mouse hearts. In addition, histological analysis, immunofluorescence, and western blot results showed that Sac/Val attenuated cardiac fibrosis and inflammation after DB. Finally, our data indicated that Sac/Val treatment could significantly suppress NF-κB signaling and NLRP3 inflammasome activation in mice after relief of pressure overload. Conclusion Sac/Val exerted its beneficial effects to prevent maladaptive cardiac fibrosis and dysfunction in mice following pressure unloading, which was at least partly due to the inhibition of NLRP3 inflammasome activation. |
Databáze: | OpenAIRE |
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