αv vitronectin receptors in vascular‐mediated disorders

Abstract

Various integrin antagonist candidates including antibodies, cyclic peptides, peptidomimetics, and non-peptides have been clinically evaluated and shown to successfully modulate certain disease processes. This review will focus on the key role of the alphav integrin (alphavbeta3 and alphavbeta5) in vascular disorders such as restenosis and angiogenesis-mediated disorders.

Vitronectin Concentrations Predict Risk in Patients Undergoing Coronary Stenting

“…14 -16 Vitronectin and sVNR are present in human atheromatous plaques, suggesting that they may be implicated in atherosclerosis and restenosis. [17][18][19][20] Plasma vitronectin levels were significantly increased in patients with coronary artery diseases, showing a positive correlation with severity of the disease. 21 Using data from a randomized, placebo-controlled trial of abciximab in patients undergoing percutaneous coronary intervention, we tested the hypothesis that patient serum concentrations of vitronectin and sVNR correspond with cardiovascular outcomes at 30 days and 6 months following revascularization.…”

“…14,25 The vitronectin ␣ v ß 3 receptor is not only widely expressed on endothelial and smooth muscle cells, but also on platelets, macrophages, and neutrophils. 26 Endothelial cells in the microvessels of atherosclerotic plaques exhibit high vitronectin receptor expression. Besides vitronectin, other ligands such as fibrinogen, thrombospondin, and prothrombin also bind to the vitronectin receptor.…”

Targeting of αv integrins interferes with FAK activation and smooth muscle cell migration and invasion

“…Immediately after the intervention, an early inflammatory response characterized by the recruitment and adhesion of leucocytes, macrophages, and activated platelets to the site of the vessel injury can be observed. In addition to various growth factors and cytokines released locally by resident and recruited cells, plasma proteins such as vitronectin, osteopontin, and fibronectin are deposited at the site of the lesion [4][5][6][7]. A combination of these chemotactic and haptotactic stimuli drives the proliferation and migration of vascular cells, mainly smooth muscle cells (SMCs), leading to their accumulation in the newly formed neointima.…”

Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs

“…The role of different amino acids in providing hydrogen bonding and interactions within the propeller region of αV subunit for larger length molecules was clearly different than for shorter length molecules, that is, tetrac. This was a further indication of a dual role of the integrin receptor, via both integrin ligand and thyroid binding domains, as a thyrointegrin receptor with transactivation capabilities, and a strong indication that the designed compounds would have bifunctional activity as integrin inhibitors and thyroid antagonists 60,[67][68][69][70][71][72][73] . The in silico binding of the designed compounds and superimposition of their binding orientations with peptide ligands, tetrac, and XT199 antagonist again showed the effective geometry of the compounds 9, 10, and 11 to be shorter than those in peptides and XT199 due to the perpendicular twisted geometry of the adjacent phenyl rings linked and manoeuvrable through an ether bond.…”