In a successful wound healing event, endothelial cells adjacent to a site of mechanical wound must perceive that an injury has occurred; migrate into the region; proliferate to restore the flawed area; and finally, return to a nonproliferative state. This process involves the regulation of many genes. To elucidate these genes, an in vitro wound healing model using endothelial cell cultures, maintained on an artificial basement membrane of type IV collagen, is being developed. Differential display will be utilized to isolate and identify mRNAs that are regulated during this wound healing process. This approach, along with the use of an in vivo model of infective endocarditis, may provide insights into the disease mechanisms underlying the healing of injured or diseased heart valves which may become the site for the development of platelet vegetations. Differential gene regulation during wound healing of this relatively avascular, collagenous valve tissue, may play a key role determining whether repair or vegetation formation occurs.