Presentation Abstract

Session: 10-Outstanding Early Career Award Finalists
Wednesday, Jul 24, 2013, 1:00 PM - 1:45 PM
Presentation: 358 - Transient Receptor Potential Vanilloid 2 (TRPV2) contributes to myocardial contractility and hypertrophy via sarcoplasmic reticulum calcium handling
Location: Concorde B/C
Pres. Time: Wednesday, Jul 24, 2013, 1:00 PM - 1:15 PM
Category: Contractility and Calcium-Handling
Keywords: Contractile function; Hypertrophy; Calcium handling
Author(s): Jack Rubinstein, Vivek P. Singh, Valerie M Lasko, Sheryl E Koch, Evangelia Kranias, W. Keith Jones, John N Lorenz, Univ of Cincinnati, Cincinnati, OH
Abstract: Background. TRPV2 is a Ca2+ channel that we have recently discovered in cardiomyocytes. The absence of this channel negatively impacts baseline contractility while stimulation results in a positive inotropic response. What remains to be established is the mechanism of this receptor and its role, if any, in the development of hypertrophy.
Methods and Results. We obtained isolated cardiomyocytes from wild type (WT) and TRPV2-/- (KO) mice and found that the sarcoplasmic reticulum Ca2+ content and Ca2+ transients were reduced along with fractional shortening in the KO cardiomyocytes (figure, panels A, B, C). In vivo echocardiography confirmed a decrease in ejection fraction in KO mice in comparison to the WT counterparts (panel D).
The relevance of these findings was examined in 6 WT and 5 KO mice subjected to transverse aortic constriction (TAC). These mice were followed by echocardiography weekly for a total of 8 weeks post TAC. At the conclusion, the hearts were obtained for histological and molecular analyses. We demonstrated that the KO mice developed less LV hypertrophy in comparison to WT (via echocardiography and by heart weight/body weight ratios) (figure, panels E and F). Importantly, there was a 5 fold increase in TRPV2 expression assessed by PCR in TAC WT hearts, compared to WT not subjected to TAC (0.72±0.10 vs. 0.13±0.04; p<0.01). This suggests a role for TRPV2 not only in contractility, but also in the development of hypertrophy.
Conclusions. We have discovered a novel cardiac channel that alters Ca2+ cycling and is capable of modulating cardiomyocyte contractility and hypertrophy, which could lead to novel therapeutic options in heart failure and hypertrophy.
Disclosures:   J. Rubinstein: 7. Ownership Interest; Modest; TRP Therapeutics. V.P. Singh: None. V.M. Lasko: None. S.E. Koch: None. E. Kranias: None. W. Jones: 7. Ownership Interest; Modest; TRP Therapeutics. J.N. Lorenz: None.



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