Abstract 82: Reduction of SHP2’s Phosphatase Activity Improves Cardiac Adaptation to Pressure and Volume Overload

• Published in: Circulation research 2016-07, Vol.119 (suppl_1)
• Main Authors: Roy, Rajika, Crombie, Kathryn, Douglas, Diana, Krenz, Maike
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.119.suppl_1.82

Abstract only Since the inability of the heart to adapt to pathological stress results in heart failure, supporting cardiac stress adaptation may improve clinical outcome. We hypothesized that the protein tyrosine phosphatase SHP2 controls adaptation by modulating several signaling pathways involved. To test whether SHP2 plays an active role in stress adaptation, we generated transgenic (TG) mice with cardiomyocyte-specific overexpression of Q510E-SHP2, which is a dominant-negative mutant (dnSHP2). Under unstressed conditions, TG mice do not exhibit a cardiac phenotype. TG and nonTG (NTG) mice were subjected to pressure overload by transverse aortic constriction (TAC) or to volume overload by inducing large myocardial infarction (MI) via coronary artery ligation. Expression of dnSHP2 significantly improved stress adaptation after TAC (n=17 TG, n=13 NTG). Twelve weeks after banding, TG mice exhibited well preserved contractile function with significantly higher fractional shortening (FS) [TG 33.2±1.7 vs. NTG 22.2±1.5 %, p