Osteopontin controls endothelial cell migration in vitro and in excised human valvular tissue from patients with calcific aortic stenosis and controls

• Published in: Journal of cellular physiology 2011-08, Vol.226 (8), p.2139-2149
• Main Authors: Poggio, Paolo, Grau, Juan B., Field, Benjamin C., Sainger, Rachana, Seefried, William F., Rizzolio, Flavio, Ferrari, Giovanni
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis - physiopathology; Calcinosis - physiopathology; Cell Movement - physiology; Cells, Cultured; Endothelial Cells - physiology; Female; Humans; Male; Middle Aged; Neovascularization, Pathologic - chemically induced; Neovascularization, Pathologic - physiopathology; Osteopontin - adverse effects; Osteopontin - blood; Osteopontin - physiology
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.22549

Calcific aortic stenosis (CAS) is a pathological condition of the aortic valve characterized by dystrophic calcification of the valve leaflets. Despite the high prevalence and mortality associated with CAS, little is known about its pathogenetic mechanisms. Characterized by progressive dystrophic calcification of the valve leaflets, the early stages of aortic valve degeneration are similar to the active inflammatory process of atherosclerosis including endothelial disruption, inflammatory cell infiltration, lipid deposition, neo‐vascularization and calcification. In the vascular system, the endothelium is an important regulator of physiological and pathological conditions; however, the contribution of endothelial dysfunction to valvular degeneration at the cellular and molecular level has received little attention. Endothelial cell (EC) activation and neo‐vascularization of the cusps characterizes all stages of aortic valvular degeneration from aortic sclerosis to aortic stenosis. Here we reported the role of osteopontin (OPN) in the regulation of EC activation in vitro and in excised tissue from CAS patients and controls. OPN is an important pro‐angiogenic factor in several pathologies. High levels of OPN have been demonstrated in both tissue and plasma of patients with aortic valve sclerosis and stenosis. The characterization of valvular ECs as a cellular target for OPN will help us uncover the pathogenesis of aortic valve degeneration and stenosis, opening new perspectives for the prevention and therapy of this prevalent disease. J. Cell. Physiol. 226: 2139–2149, 2011. © 2010 Wiley‐Liss, Inc.