Heart failure represents a major cause of morbidity and mortality in the United States. The current model of heart failure postulates that neurohumoral activation contributes to the progression of left ventricular dysfunction to clinical heart failure. Chronic beta adrenergic receptor stimulation is believed to contribute to heart failure by causing increased cardiac myocyte apoptosis. Specifically, beta 1 receptors are believed to couple to a pro-apoptotic pathway in myocytes. Recent studies have shown that beta 2 receptor may also couple to an antiapoptotic pathway that promotes myocyte survival. The goal of this project is to analyze beta receptor signaling pathways in cardiac myocytes using a proteomic technology termed reverse phase protein (RPP) lysate microarrays. RPP microarrays allow for the simultaneous measurement of diverse phosphoprotein signaling cascades.
The first aim will study a time course of beta receptor signaling in neonatal cardiac myocytes using RPP microarrays.
The second aim i s to dissect the role of the individual beta receptor subtypes by using neonatal myocytes derived from knockout mice.
The third aim of the project is to correlate these findings with studies on whole hearts from an animal model of heart failure.
