Abstract
Cardiovascular diseases (CVD) remain a major worldwide health problem and we propose an integrated Translational Approach that relies on genetic strategies to disassemble complex phenotypes and determination of the molecular underpinning of gene variants on cardiac and vascular phenotypes. The main goals of this proposal are to 1. Identify the molecular underpinning of cardiovascular diseases (CVD) or phenotypes and 2. Establish targeted therapeutics for CVDs. This will be accomplished by development of nine interconnected projects to address 1. The identification of genetic determinants of hypertension; 2. The mechanisms whereby physical forces (shear-stress and strain) influence vascular homeostasis and disease states; 3. Whether the adult cardiac regenerative capacity can be therapeutically modulated or replaced by a cell type approach to halt disease progression; and 4. How genetic variants do influence CV risk and outcomes. The proposal has a broad scope and shall catalyze incremental-type discoveries as well as high risk endeavors that may be translated into novel ways to predict events and to take preemptive steps to avoid irreversible damage or improve organ regeneration in cardiovascular medicine. (AU)
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