Expression and function of PIGF in cardiomyocytes

Drake University, Des Moines IA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Myocardial ischemia/infarction is a leading cause of morbidity and mortality in the United States. Although therapies to enhance coronary angiogenesis and reduce myocyte cell death could substantially reduce the severity of ischemic heart disease, the endogenous mechanisms promoting blood vessel growth in the heart are not known. One hypothesis involves the production of specific factors from cardiomyocytes that then either act in a paracrine "fashion to induce the growth of the surrounding vasculature and/or act in an autocrine manner to protect the cells from apoptosis. A greater understanding of the expression and modulation of these endogenous growth factors and their receptors in the heart is clearly warranted. The long-term goal of our research is to define the expression and modulation of placenta growth factor (PIGF) in heart tissue. PIGF has been shown to act synergistically with vascular endothelial growth factor (VEGF) to promote angiogenesis and inhibit apoptosis. We and others have shown significant upregulation of VEGF expression in models of coronary angiogenesis however, quantitative changes in PIGF expression are not known. In addition, there is little information regarding the regulation and function of endogenous PIGF in heart tissue. Our central hypothesis is that myocardial PIGF expression is increased during ischemia and provides a key plays a key survival advantage for cardiomyocytes by potentiating VEGF's angiogenic effect and by directly protecting the cells from ischemia-induced apoptosis. These hypotheses will be tested according to the following specific aims: 1) Establish the relationship between ischemia-induced or stretch-induced models of coronary angiogenesis and expression of PIGF and its receptors in vivo. 2) Determine the relative contribution of hypoxia and mechanical stretch on expression of PIGF and its receptors in cultured rat cardiomyocytes. 3) Determine the functional role of endogenous PIGF by determining its ability to protect cardiomyocytes from hypoxia/reoxygenation-induced apoptosis in vitro. Results from these studies will provide novel information regarding the expression, modulation and function of endogenous PIGF and its receptors in cardiac tissue. Collectively, these data may provide support for PIGF-mediated therapeutic approaches to facilitate coronary microvascular growth and/or reduce the cardiomyocyte loss associated with ischemic heart disease. [unreadable] [unreadable]