G protein-coupled receptors such as adrenergic receptors (ARs) are critical to heart function. Alpha1-ARs, coupling to the G protein Gq, as well as other Gq-coupled receptors have been implicated in myocardial hypertrophy. Studies in mice have indicated that Gq is a common trigger initiating left ventricular (LV) hypertrophy following pressure overload. The current proposal is centered on right ventricular (RV) hypertrophy and failure, which is of clinical significance (e.g. increased RV afterload via PA stenosis). We are interested in studying the signaling mechanisms involved in RV hypertrophy following an acute and chronic model of PA banding. The proposal examines whether adenoviral-mediated intracoronary gene delivery of GqI to the RV of adult rabbits can attenuate the progression of hypertrophy, dilatation and dysfunction that accompany increased RV afterload. The Central Hypothesis is that Gq is a key figure in the RV hypertrophic response and contributes to the pathogenesis of RV dysfunction and heart failure, and that myocardial gene transfer of a peptide inhibitor of Gq signaling will mitigate the hypertrophic response in the RV following PA banding and improve the acute and chronic biochemical and physiological function of the hypertrophied heart.
| Parsa, Cyrus J; Kim, Jihee; Riel, Ryan U et al. (2004) Cardioprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiac fibroblasts. J Biol Chem 279:20655-62 |
| Parsa, Cyrus J; Matsumoto, Akio; Kim, Jihee et al. (2003) A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 112:999-1007 |
