The purpose of the proposed project is to evaluate those properties of blood vessels which affect their thrombogenicity. In addition, recent observations from our laboratory have led us to an interest in the relationship between vessel injury and the pathogenesis of atherosclerosis. The following experiments are planned, with rabbits as the main experimental animal. 1. Preliminary observations have suggested that intimal glycoproteins "insulate" active connective tissues, therby rendering them less thrombogenic. The nature of these materials, and their variability with site and disease will be explored. 2. Studies will be performed relating the effects of long-term estrogen or androgen administration to vessel thrombogenicity and healing response. 3. We have identified tissue factor (thromboplastin) antigen as being uniquely present on endothelial cell plasma membrane in normal tissues. Studies are planned to evaluate its distribution in healing tissues, and particularly in proliferating endothelial cells. 4. When an injured vessel heals, marked intimal thickening occurs. Experiments will be performed to determine the factors controlling this proliferative response. Particular attention will be given to endothelial permeability, and identification of the cells lining the neoendothelium.