Vascular Expression of Integrin-Associated Protein and Thrombospondin Increase After Mechanical Injury

• Published in: Journal of investigative medicine Vol. 49; no. 5; pp. 398 - 406
• Main Authors: Sajid, Mansoor, Hu, Zhaoyong, Guo, Huiping, Li, Husong, Stouffer, George A.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.09.2001; Sage Publications Ltd; SLACK INCORPORATED
• Subjects: Animals; Antigens, CD - biosynthesis; Blood Vessels - injuries; Carrier Proteins - biosynthesis; CD36 Antigens - biosynthesis; CD47 Antigen; Cell Division - drug effects; Cells, Cultured; Humans; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Papio; Thrombospondins - biosynthesis; Wound Healing; thrombospondin; vitronectin; receptors; muscle; extracellular matrix; angioplasty; smooth
• ISSN: 1081-5589; 1708-8267
• DOI: 10.2310/6650.2001.33784

BackgroundIntegrin-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.MethodsLeft 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).ResultsWe 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.ConclusionsVascular 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.