The objectives of this proposal are to understand the factors which are important for the initiation of smooth muscle cell replication which occurs after arterial injury. In particular, the studies proposed will focus on the role of basic FGF as it pertains to the replication of smooth muscle cells in an injured artery. Experiments will focus on why bFGF, which is a potent mitogen for smooth muscle cells of an injured artery, does not stimulate smooth muscle cells of uninjured arteries, and will ask if bFGF requires the interaction of other growth factors to function as an in vivo mitogen. Other experiments related to this question will provide evidence of FGF receptor expression by arterial smooth muscle cells both prior to and after injury and whether access of exogenous bFGF into an uninjured arterial wall is limited. Other experiments will investigate if injury and the action of other growth factors will induce expression of an FGF receptor. Another group of studies will determine whether bFGF plays an important role for the ongoing smooth muscle cell replication which occurs for several weeks after a single balloon injury and will determine if the smooth muscle cells of intimal lesions synthesize bFGF. A final group of experiments will develop a model of injury to existing intimal lesions in rat arteries and then ask if the smooth muscle cell growth which occurs after injury to these intimal lesions (i.e., angioplasty) is dependent on either bFGF synthesis or its release from these intimal smooth muscle cells.
Showing the most recent 10 out of 50 publications
