TRPV4 deletion protects heart from myocardial infarction-induced adverse remodeling via modulation of cardiac fibroblast differentiation.

TRPV4 deletion protects heart from myocardial infarction-induced adverse remodeling via modulation of cardiac fibroblast differentiation.

Adapala Ravi K; Kanugula Anantha K; Paruchuri Sailaja; Chilian William M; Thodeti Charles K

Basic research in cardiology

2020

2020-01

Cardiac fibrosis caused by adverse cardiac remodeling following myocardial infarction can eventually lead to heart failure. Although the role of soluble factors such as TGF-beta is well studied in cardiac fibrosis following myocardial injury, the physiological role of mechanotransduction is not fully understood. Here, we investigated the molecular mechanism and functional role of TRPV4 mechanotransduction in cardiac fibrosis. TRPV4KO mice, 8 weeks following myocardial infarction (MI), exhibited preserved cardiac function compared to WT mice. Histological analysis demonstrated reduced cardiac fibrosis in TRPV4KO mice. We found that WT CF exhibited hypotonicity-induced calcium influx and extracellular matrix (ECM)-stiffness-dependent differentiation in response to

Mechanotransduction; TRPV4; Myocardial infarction; Myocardial infarction; TGF-beta1; Rho/Rho kinase; Mechanotransduction; TGF-β1; Myocardial infarction; EXTRACELLULAR matrix; HEART failure; HEART fibrosis; HEART; Cardiac fibroblast; Cardiac fibrosis; Rho/Rho kinase; TRPV4; Cardiac fibroblast; Cardiac fibrosis; DELETION mutation

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Journal Article

14-14

2

115

NEOMED College of Medicine

Department of Integrative Medical Sciences

March 2020 Update