BACKGROUND: Integrin-associated protein (IAP) is a thrombospondin (TSP)-binding, Gi protein-coupled cell surface receptor. The vascular function of IAP has not been defined, and it is not known whether TSP and IAP are expressed at the same time in injured arteries. METHODS: Left brachial arteries of baboons were injured using balloon withdrawal technique. Arteries were harvested 1 week after injury, and immunohistochemistry and in situ hybridization were performed using standard techniques. Uninjured right brachial arteries served as a control. Proliferation studies were performed using cultured human aortic smooth muscle cells (SMC). RESULTS: We found significant IAP expression in the media and neointima 7 days after injury using BRIC-126, an immunoglobulin (Ig) G2b monoclonal antibody that recognizes IAP with high specificity. In contrast, IAP staining in the uninjured vessel was only observed in the endothelium. Concurrent with IAP expression, TSP mRNA and protein expression in the neointima and media was enhanced 1 week after injury. In cultured SMC, activation of IAP was 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 vascular healing responses.
BACKGROUND:Integrin-associated protein (IAP) is a thrombospondin (TSP)-binding, Gi protein-coupled cell surface receptor. The vascular function of IAP has not been defined, and it is not known whether TSP and IAP are expressed at the same time in injured arteries. METHODS: Left brachial arteries of baboons were injured using balloon withdrawal technique. Arteries were harvested 1 week after injury, and immunohistochemistry and in situ hybridization were performed using standard techniques. Uninjured right brachial arteries served as a control. Proliferation studies were performed using cultured human aortic smooth muscle cells (SMC). RESULTS: We found significant IAP expression in the media and neointima 7 days after injury using BRIC-126, an immunoglobulin (Ig) G2b monoclonal antibody that recognizes IAP with high specificity. In contrast, IAP staining in the uninjured vessel was only observed in the endothelium. Concurrent with IAP expression, TSP mRNA and protein expression in the neointima and media was enhanced 1 week after injury. In cultured SMC, activation of IAP was 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 vascular healing responses.
Authors: Natalya V Narizhneva; Olga V Razorenova; Eugene A Podrez; Juhua Chen; Unni M Chandrasekharan; Paul E DiCorleto; Edward F Plow; Eric J Topol; Tatiana V Byzova Journal: FASEB J Date: 2005-04-15 Impact factor: 5.191
Authors: Laura A Maile; Lee B Allen; Christopher F Hanzaker; Katherine A Gollahon; Paul Dunbar; David R Clemmons Journal: Exp Diabetes Res Date: 2010-06-20
Authors: David R Soto-Pantoja; Erica V Stein; Natasha M Rogers; Maryam Sharifi-Sanjani; Jeffrey S Isenberg; David D Roberts Journal: Expert Opin Ther Targets Date: 2012-10-27 Impact factor: 6.902