Project 171429

When arteries fill with lipid because of atherosclerotic disease, blood flow can becomes severely restricted. In the case of the heart, this can lead to a heart attack. If these lipid-filled lesions are detected before a heart attack occurs, blood flow can be restored by either angioplasty (also insertion of a stent into the artery) or by bypass graft surgery. In both cases, the vessel is physically injured during the procedure. Just like a cut to the skin, an exaggerated scar can form, and this will block blood flow as badly as the original lesion. Formation of this second lesion in response to injury is called restenosis. This lab has been studying the problem of restenosis, with the aim of identifying specific processes that affect the lesion size, for several years. We have found that two hormones (angiotensin II and platelet-derived growth factor) released by the artery itself or platelets that bind to the site of damage have a significant impact on restenosis. Our studies have also found a common mediator for signals originating from these hormones. Our intention is to further characterize the mechanism by which this mediator, termed cyclic AMP response element binding protein or CREB, operates. A particular emphasis for our studies will be the connection between angiotensin II and protein kinase A, which we believe to be the primary activator of CREB. We anticipate that completing this investigation will give us more information to identify methods capable of preventing restenosis and thus prolonging the health of these individuals.

characterizing the role of CREB in vascular smooth muscle cell phenotype modulation by angiotensin II, with a focus on protein kinase A