Osteopontin, a Key Mediator Expressed by Senescent Pulmonary Vascular Cells in Pulmonary Hypertension

• DOI: 10.1161/atvbaha.116.307839
• Publication Date: 2016-07-22T02:54:06Z
• Authors: Mirna Saker; Larissa Lipskaia; Elisabeth Marcos; Shariq Abid; Aurelien Parpaleix; Amal Houssaini; Pierre Validire; Philippe Girard; Hiba Noureddine; Laurent Boyer; Nora Vienney; Valerie Amsellem; Laurent Marguerit; Bernard Maitre; Geneviève Derumeaux; Jean-Luc Dubois-R...; Claude Jourdan-Le...; Marion Delcroix; Rozenn Quarck; Serge Adnot
• Keywords: Osteopontin; Pathogenesis; Senescence; Nitrotyrosine; Immunostaining

Senescent pulmonary artery smooth muscle cells (PA-SMCs) may contribute to the pathogenesis of hypertension by producing secreted factors. The aim this study was explore role in extracellular matrix proteins released senescent PA-SMCs.Polymerase chain reaction array analysis human PA-SMCs undergoing replicative senescence revealed osteopontin upregulation, which mediated stimulatory effect PA-SMC media and on growth migration. Osteopontin upregulated lungs from patients with chronic obstructive disease or idiopathic arterial hypertension. Prominent immunostaining noted that also stained for p16 at sites vascular hypertrophy, lung levels correlated closely age. Compared younger mice, 1-year-old mice displayed higher levels, right ventricular systolic pressure, vessel muscularization, numbers p21 osteopontin. No such changes age were observed osteopontin(-/-) developed attenuated during hypoxia. cultured young grew faster; a similar fast rate seen stimulated old mice. Differences between old/young mouse rates suppressed antiosteopontin antibodies. more slowly than did wild-type PA-SMCs; they matrix, stronger older versus mice.Osteopontin is key mediator contributing progression.