title: Cardiac-specific overexpression of caveolin-3 attenuates cardiac hypertrophy and increases natriuretic peptide expression and signaling.
abstract: OBJECTIVE
  We hypothesized that cardiac myocyte-specific overexpression of caveolin-3 (Cav-3), a muscle-specific caveolin, would alter natriuretic peptide signaling and attenuate cardiac hypertrophy.
  
  
  BACKGROUND
  Natriuretic peptides modulate cardiac hypertrophy and are potential therapeutic options for patients with heart failure. Caveolae, microdomains in the plasma membrane that contain caveolin proteins and natriuretic peptide receptors, have been implicated in cardiac hypertrophy and natriuretic peptide localization.
  
  
  METHODS
  We generated transgenic mice with cardiac myocyte-specific overexpression of caveolin-3 (Cav-3 OE) and also used an adenoviral construct to increase Cav-3 in cardiac myocytes.
  
  
  RESULTS
  The Cav-3 OE mice subjected to transverse aortic constriction had increased survival, reduced cardiac hypertrophy, and maintenance of cardiac function compared with control mice. In left ventricle at baseline, messenger ribonucleic acid for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were increased 7- and 3-fold, respectively, in Cav-3 OE mice compared with control subjects and were accompanied by increased protein expression for ANP and BNP. In addition, ventricles from Cav-3 OE mice had greater cyclic guanosine monophosphate levels, less nuclear factor of activated T-cell nuclear translocation, and more nuclear Akt phosphorylation than ventricles from control subjects. Cardiac myocytes incubated with Cav-3 adenovirus showed increased expression of Cav-3, ANP, and Akt phosphorylation. Incubation with methyl-β-cyclodextrin, which disrupts caveolae, or with wortmannin, a PI3K inhibitor, blocked the increase in ANP expression.
  
  
  CONCLUSIONS
  These results imply that cardiac myocyte-specific Cav-3 OE is a novel strategy to enhance natriuretic peptide expression, attenuate hypertrophy, and possibly exploit the therapeutic benefits of natriuretic peptides in cardiac hypertrophy and heart failure.
authors: Department of Anesthesiology, University of California, San Diego, La Jolla, California, USA.
authors: Yousuke T
authors: YT
authors: Horikawa
authors: Mathivadhani
authors: M
authors: Panneerselvam
authors: Yoshitaka
authors: Y
authors: Kawaraguchi
authors: Yasuo M
authors: YM
authors: Tsutsumi
authors: Sameh S
authors: SS
authors: Ali
authors: Ravi C
authors: RC
authors: Balijepalli
authors: Fiona
authors: F
authors: Murray
authors: Brian P
authors: BP
authors: Head
authors: Ingrid R
authors: IR
authors: Niesman
authors: Timo
authors: T
authors: Rieg
authors: Volker
authors: V
authors: Vallon
authors: Paul A
authors: PA
authors: Insel
authors: Hemal H
authors: HH
authors: Patel
authors: David M
authors: DM
authors: Roth
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