Proliferative cardiovascular diseases such as atherosclerosis and restenosis are a major cause of death in the western world in general and in the United States in particular. Inflammation that follows vascular injury is believed to be important in the initiation and progression of atherosclerosis and restenosis. Several events can be triggered as c consequence of inflammation at the site of arterial injury. These are 1) lipid peroxidation, 2) arterial smooth muscle cell (SMC) growth induction, and 3) angiogenesis. All these events are characteristic of atherosclerosis and restenosis. Phospholipase A2s (PLA2s), a group of enzymes that break down membrane phospholipids generating arachidonic acid and lysophospholipids have been implicated in inflammation process. We hypothesize that PLA2 plays a critical role in the above described events leading to atherosclerosis and restenosis. To test this, we will address three specific aims: 1) determine the role and type of PLA2 in growth factor-induced arachidonic acid release and mitogenesis in SMC, 2) study the effects of various growth factors on eicosanoid production and determine the role of eicosanoids in mitogenic signaling events induced by these agonists, and 3) mechanisms. The results of this proposal will provide new information in regard to the role of PLA2 and eicosanoids in the modulation of SMC growth and angiogenesis, the important events in the pathogenesis of atherosclerosis and restenosis and provide rationale to design drugs in the prevention of progression of these vascular lesions.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Experimental Cardiovascular Sciences Study Section (ECS)
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University of Tennessee Health Science Center
Internal Medicine/Medicine
Schools of Medicine
United States
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