TRPV4 deletion improves cardiac function, structure and remodeling following myocardial infarction

Ischemic heart disease (IHD) is the major underlying cause of myocardial infarction (MI), scarring, and hypertrophy leading to heart failure. The prevention of ischemic damage due to MI involves scar formation by synthesis and reorganization of ECM. Cardiac fibroblasts are the primary mediators of cardiac repair as they secrete and remodel extracellular matrix in the heart. We have recently demonstrated that mechanosensitive ion channel, TRPV4 (Transient Receptor Potential Vanilloid 4) mediates cardiac fibroblast differentiation into myofibroblasts in vitro . However, the physiological significance of TRPV4 in cardiac remodeling in vivo is not known. In the present study, we explored the role of TRPV4 in cardiac remodeling following MI. We subjected WT and TRPV4KO mice to MI (permanent occlusion of LAD) and measured cardiac function for 8 weeks by serial echocardiographic assessment. We found significant time‐dependent preservation of cardiac function (ejection fraction and fractional shortening) post‐MI in TRPV4KO mice compared to WT counterparts. Further, picro‐sirius red and Masson's trichrome staining revealed reduced collagen deposition in infarcted and remote zones of TRPV4KO hearts, 8 weeks post‐MI. Mechanistically, we found decreased cardiomyocyte apoptosis (TUNEL assay) and increased capillary density (CD31 staining) in TRPV4KO hearts compared to WT hearts, 1 week post‐MI. Taken together, these results suggest that absence of TRPV4 preserves cardiac function and structure post‐MI by reducing myocyte apoptosis and cardiac fibrosis probably by increasing revascularization. Support or Funding Information NIH(1RO1HL119705)NIH(1R15CA202847‐01), AHA Grant in Aid(14GRNT20380935)