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Temple scientists receive $11.5 million grant for heart failure research
Date:5/22/2014

veloped highly integrated research programs aimed at better understanding the signaling molecules involved in heart failure. Their preliminary research resulted in the identification of the three signaling pathways that the researchers are now investigating for the second PPG. Those pathways center on an enzyme known as G-protein coupled receptor kinase 5 (GRK5) and on molecules known as arginine vasopressin (AVP) type 1A receptors and transient receptor potential (TRP) channels.

GRK5 forms the basis of Dr. Koch's portion of the PPG. In earlier work, he and colleagues found that the enzyme, which normally resides in the cytoplasm of heart cells, can be transported into the heart cell nucleus. There, in the cockpit of the cell, GRK5 takes control over the activity of certain genes. Its manipulations ultimately cause heart cells to increase in size, creating a condition known as hypertrophy, which is a central feature of heart failure.

Dr. Feldman's PPG research explores the role of AVP type 1A receptors in cardiac injury. In previous work in mice, Feldman's team found that the density of AVP receptors increases in the heart following cardiac injury. The change in receptor expression was associated with diminished heart function. In the next steps of investigation, Feldman hopes to elucidate the mechanism underlying that association.

Dr. Houser's project is focused on TRP channels and the role of calcium signaling in cardiac hypertrophy and tissue remodeling in heart failure. Following ischemia, which temporarily deprives the heart of oxygen, TRP channels are expressed at abnormally high levels. Dr. Houser suspects that the change in channel expression increases calcium entry into heart cells, leading to maladaptive remodeling processes such as hypertrophy.

The suspected point of intersection for the three pathways is with AVP receptor signaling. Activation of AVP receptors mediates heart cell damage during cardiac injury but may al
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Contact: Jeremy Walter
Jeremy.Walter@tuhs.temple.edu
215-707-7882
Temple University Health System
Source:Eurekalert

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