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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001533-05
Application #
3081897
Study Section
(SRC)
Project Start
1984-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1988-06-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
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