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Cardiac myocyte‐specific caveolin‐3 overexpression modulates ANP production and attenuates cardiac hypertrophy in vivo
Author(s) -
Horikawa Yousuke T,
Tsutsumi Yasuo M,
Patel Hemal H,
Roth David M
Publication year - 2009
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.23.1_supplement.576.10
Subject(s) - atrial natriuretic peptide , medicine , caveolae , myocyte , cardiac myocyte , endocrinology , caveolin 3 , cardiac function curve , muscle hypertrophy , in vivo , biology , heart failure , microbiology and biotechnology , signal transduction
The organization of signaling molecules in cardiac hypertrophy are incompletely understood. Caveolae, invaginations of the sarcolemmal membrane localize signaling molecules involved in cardiac hypertrophy. Atrial naturetic peptide (ANP) regulates endothelin‐1 release and cardiac hypertrophy. Furthermore, ANP is secreted via and stored within caveolae. We hypothesized that cardiac myocyte‐specific overexpression of Cav‐3 (Cav‐3 OE) modulates ANP production attenuating cardiac hypertrophy in vivo. Methods Cav‐3 OE and littermate controls (C) were subjected to transverse aortic constriction (TAC) for 4 weeks. Echocardiography, histology and molecular analysis were performed. Results Cav‐3OE mice had reduced heart weights post TAC compared to C. Furthermore, Cav‐3 OE and C mice had similar fractional shortening (FS) pre TAC but had greater FS compared to C post TAC. mRNA levels of ANP were 7‐fold greater in Cav‐3 OE at baseline compared to C, resulting in increased protein expression of ANP in the cardiac myocyte and blood. Disruption of caveolae with colchicine in adult cardiac myocytes isolated from Cav‐3 OE resulted in a decrease in ANP. Conclusion We show that Cav‐3 OE alters ANP production in cardiac myocytes blunting cardiac hypertrophy while preserving cardiac function post TAC. This suggests a therapeutic role for overexpression of Cav‐3 in pathological cardiac hypertrophy.