Atherosclerosis and restenosis after therapeutic interventions are characterized by smooth muscle cell (SMC) accumulation and extracellular matrix (ECM) deposition in the vessel wall. Growth factor production seems to play a role in the initiation of these processes, but the role of growth factors in the long-term response to injury is unknown. The investigators propose that basic fibroblast growth factor (bFGF) is important in not only the immediate response of the arterial wall to injury, but also in the chronic response. They hypothesize that after injury, there are distinct activities of bFGF and FGF receptor (FGFR), such that delivery into the artery wall of an adenoviral vector encoding antisense to bFGF (ASbFGF) or a kinase defective, dominant negative bFGF receptor (dnFGFR-1) will alter the activity of bFGF or its receptor in the arterial wall, and thereby modify the arterial response to injury. To test this hypothesis injured rat carotid arteries will be infected with an adenoviral vector encoding ASbFGF or dnFGFR-1. The expression of bFGF ligand or its receptor will be compared with controls. In addition, the consequence of infection with ASbFGF or dnFGFR-1 will be assessed in terms of SMC proliferation, migration, apoptosis, and ECM deposition and wall thickening. This should yield a better understanding of the response of the artery wall to injury and the role of bFGF in the process. This will allow more directed approaches to control the pathologic process by manipulating bFGF signaling.
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