Vascular expression of integrin-associated protein and thrombospondin increase after mechanical injury

Background. Integrin-associated protein (IAP) is a thrombospondin (TSP)-bin ding, G(i) protein-coupled cell surface receptor. The vascular function of IAP has not been defined, and it is not known whether TSP and IAP are expre ssed at the same time in injured arteries. Methods: Left brachial arteries of baboons were injured using balloon withd rawal technique. Arteries were harvested 1 week after injury, and immunohis tochemistry and in situ hybridization were performed using standard techniq ues. Uninjured right brachial arteries served as a control. Proliferation s tudies were performed using cultured human aortic smooth muscle cells (SMC) . Results: We found significant IAP expression in the media and neointima 7 d ays after injury using BRIC-126, an immunoglobulin (I-g) G(2b) monoclonal a ntibody that recognizes IAP with high specificity. In contrast, IAP stainin g in the uninjured vessel was only observed in the endothelium. Concurrent with IAP expression, TSP mRNA and protein expression in the neointima and m edia was enhanced I week after injury. In cultured SMC, activation of IAP w as sufficient to elicit a proliferative response. TSP-induced proliferation was inhibited by antibodies that block TSP binding to IAP and mimicked by 4N1K, a 10-amino acid peptide derived from the IAP binding site within the carboxyl terminus of TSP. Conclusions: Vascular expression of IAP and TSP increased after mechanical injury and activation of IAP elicited a proliferative response in cultured SMC. These findings support the hypothesis that IAP participates in vascula r healing responses.