Platelet alpha granules contain a smooth muscle cell mitogen which is secreted during platelet attachment to vascular surfaces and may be important in the pathogenesis of atherosclerosis; in addition, intravascular platelet aggregation is an important cause of the clinical symptoms of the atherosclerotic vascular disease. The studies described here are designed to elucidate the interaction of platelets with the arterial wall. To do so, we will utilize a rabbit and rat model of vascular disease in which the aortic endothelium is removed with a balloon catheter. Platelet attachment will be quantitated by use of 51Cr labeled platelets and platelet alpha granule secretion into the vessel wall will be followed by indirect immunofluorescent staining for Platelet Factor 4. We will study the kinetics of platelet attachment and secretion after injury by interrupting these events with prostacyclin. In addition, using a sensitive assay for vascular smooth muscle cell DNA-specific activity we will determine if this effect of prostacyclin can inhibit smooth muscle cell proliferation after vascular injury. These findings will be closely correlated with electron and light microscopic study of the vessel wall and surface. Injury of the neointima which forms after de-endothelialization results in a complicated surface reaction characterized by platelet attachment and fibrin deposition that closely mimics the events occurring on an advanced human atherosclerotic plaque. By using the above-mentioned techniques and 125I labeled fibrinogen we will examine the thrombotic nature of the neointima and determine its ability to activate plasminogen. Finally, these technqieus will be applied to the study of vascular hoemostasis in senescent and diabetic animals.
| Asch, A S; Adelman, B; Fujimoto, M et al. (1988) Identification and isolation of a platelet GPIb-like protein in human umbilical vein endothelial cells and bovine aortic smooth muscle cells. J Clin Invest 81:1600-7 |
| Sobel, M; Adelman, B; Greenfield, L J (1986) Dextran 40 reduces heparin-mediated platelet aggregation. J Surg Res 40:382-7 |
