Localization of vitronectin in the normal and atherosclerotic human vessel wall

Abstract

Vitronectin (Vn) regulates proteolytic enzyme systems, as well as cell migration and tissue remodelling. These processes have been implicated in the pathogenesis of atherosclerosis. In this study, the distribution of Vn antigen in apparently normal and atherosclerotic human blood vessels was evaluated. Normal and diseased vessels showed Vn immunostaining in the lamina elastica interna and externa, and in strand-like structures in the adventitia. In most of these instances, the Vn antigen appeared to be located in the proximity of elastin. In pulmonary arteries, Vn staining was additionally detected in the media. The intima was devoid of Vn antigen in all vessels studied. In general, there was increased deposition of Vn antigen in the atherosclerotic arteries. In particular, strong Vn staining was apparent in amorphous material adjacent to cholesterol clefts and in acellular fibrous tissue, in plaques present in the carotic artery and aorta. Collagen layers and fresh fibrin depositions were devoid of Vn antigen. In spite of the abundance of Vn immunostaining throughout the normal and diseased vessel wall, the Vn transcript was not detectably by in situ hybridization. These results indicate that Vn is a constituent of the normal vessel wall and raise the possibility that increased local deposition of Vn may be related to the development of atherosclerotic vascular disease.

Molecular Interactions and Functional Interference between Vitronectin and Transforming Growth Factor-β

“…Furthermore, comparison of growth factor binding to the different VN isoforms revealed that multimeric forms of VN (predominantly present in the ECM and secreted by platelets) exhibit higher affinity than plasma VN for TGF-␤. Heparin-binding VN multimers are thought to be the major reactive forms of the adhesive protein in connective tissue or on cell surfaces and may become deposited in the vessel wall upon vascular injury or during aging (Dufourcq et al, 1998;Mullins et al, 2000;Preissner 1991;Van Aken et al, 1997). Thus, binding to VN can potentially increase the local concentration of a respective growth factor at the cell-ECM interface and thereby influences its functions.…”

Plasminogen Activator Inhibitor-1 Is a Major Determinant of Arterial Thrombolysis Resistance

“…12 Immunohistochemical staining for PAI-1 was performed with a Histostain-Plus kit, Zymed Laboratories, as described previously. 15 Secondary antibody was biotinylated goat anti-rabbit IgG.…”

Inhibition of Angiogenesis in Vivo by Plasminogen Activator Inhibitor-1

“…Vitronectin is a multifunctional glycoprotein present in plasma, platelets, and the extravascular matrix. Like PAI-1, vitronectin is deposited at sites of disease or injury (15,16), where it binds multiple ligands, including collagens, fibrin, uPA receptor, integrins, and PAI-1 (17)(18)(19)(20)(21). Plasma vitronectin is in a closed conformation that does not interact with integrins.…”