Premium
Absence of TRPV4 Channels Improves Cardiac Function and Remodeling Following Myocardial Infarction and Transverse Aortic Constriction
Author(s) -
Adapala Ravi K,
Luther Daniel J,
Ohanyan Vahagn A,
Luli Jordan,
Thoppil Roslin,
Paruchuri Sailaja,
Chilian William M,
Meszaros J. Gary,
Thodeti Charles K
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1129.17
Subject(s) - trpv4 , myocardial infarction , cardiac function curve , cardiology , ventricular remodeling , medicine , ejection fraction , fibrosis , heart failure , cardiac fibrosis , myofibroblast , myocardial fibrosis , ion channel , receptor
Differentiation of cardiac fibroblasts (CF) into hypersecretory and contractile myofibroblasts during cardiac remodeling leads to increased extracellular matrix (ECM) deposition and contributes to diastolic dysfunction and eventual heart failure. Recently, our work has demonstrated that a mechanosenstive ion channel, TRPV4, is involved in mediating CF differentiation into myofibroblasts, by integrating mechanical and soluble signals in vitro . In the present study we investigated the physiological significance of TRPV4 during in vivo cardiac remodeling. Wild type (WT) and TRPV4 null mice were subjected to either myocardial infarction (MI) by ligating the left anterior descending (LAD) artery or pressure overload by transverse aortic constriction (TAC). Cardiac function was analyzed by 2D and PW Doppler echocardiography while cardiac fibrosis was measured using picrosirius red staining. We found that while survival rates are unchanged in MI animals, TRPV4 null mice showed improved survival rate compared WT in mice subjected to TAC. In addition, ejection fraction was preserved in TRPV4 null mice exposed to both MI and TAC surgeries compared to WT mice and fibrosis was attenuated in the TRPV4 null hearts as well. Our findings thus suggest that the absence of TRPV4 channels improves cardiac function and remodeling following myocardial injury.