The Role of The Type III Transforming Growth Factor–beta Receptor in Epicardial Cell Behavior and Coronary Vessel Development

Abstract

Coronary artery disease accounts for 54% of all cardiovascular disease in the United States. To provide novel therapeutic targets for the prevention and treatment of coronary artery disease, my dissertation project focused on understanding the molecular mechanisms regulating coronary vessel formation during embryonic development. In particular my project focused on understanding the role of the Type III TGF-beta Receptor in regulating the behavior of epicardial cells, the precursors of coronary vessels. It was previously established that the loss of TGFâR3 in mice leads to embryonic lethality due to failed coronary vessel formation but the cellular and molecular mechanism had not been established. My project focused on identifying this mechanisms through in vitro and in vivo analysis, and uncovered that the loss of this receptor deregulates processes such as proliferation, apoptosis and invasion, which are essential to the formation of coronary vessels. We conclude from my thesis that mice lacking this receptor die in utero due to the limited number of cells available to participate in the process of coronary formation.