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
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
Externí odkaz: