Mitral valve endothelial cells secrete osteoprotegerin during endothelial mesenchymal transition

• Published in: Journal of molecular and cellular cardiology Vol. 98; pp. 48 - 57
• Main Authors: Songia, Paola, Branchetti, Emanuela, Parolari, Alessandro, Myasoedova, Veronika, Ferrari, Giovanni, Alamanni, Francesco, Tremoli, Elena, Poggio, Paolo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2016
• Subjects: Adult; Cardiovascular; Case-Control Studies; Cell Movement; Cells, Cultured; Circulating marker; Collagen - metabolism; Connective Tissue Cells - metabolism; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelial to mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression; Humans; Male; Matrix Metalloproteinases - metabolism; Mitral Valve - metabolism; Mitral Valve - pathology; Mitral valve prolapse; Mitral Valve Prolapse - diagnosis; Mitral Valve Prolapse - genetics; Mitral Valve Prolapse - metabolism; Mitral Valve Prolapse - surgery; Osteoprotegerin - genetics; Osteoprotegerin - secretion; Phenotype; Reactive Oxygen Species - metabolism; Valve endothelial cells; Valve interstitial cells; Circulating marker; Endothelial to mesenchymal transition; Valve endothelial cells; Valve interstitial cells; Mitral valve prolapse
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2016.06.061

Mitral valve prolapse (MVP) has a prevalence of 3% in the general population, affecting >176 million people worldwide. Despite this, little is known about the molecular and cellular mechanisms involved in the progression of MVP and surgical intervention is the only available option. In this study we investigated the role of osteoprotegerin (OPG) during endothelial to mesenchymal transition (EndMT) in MVP. VECs and VICs were isolated from posterior mitral valve leaflets of patients undergoing mitral valve repair (n=25). Plasma was collected from 57 subjects (29 controls and 28 MVP patients). Overexpression of OPG during EndMT followed by autocrine effects characterised by reactive oxygen species increment and accelerated migration was documented. In addition, OPG increased VIC proliferation. Finally, OPG plasma levels were significantly higher in MVP patients compared to control subjects and the area under the ROC curve was 0.92. EndMT has been recognised as a possible pathological mechanism for MVP. For the first time, we report the involvement of OPG in cellular and molecular changes in MVP isolated cells. In addition, we detected elevated circulating OPG levels in MVP patients when compared to controls, which supports the hypothesis that OPG is involved in MVP development and progression. •MVP leaflets showed higher levels of OPG than control subjects.•Endothelial-to-mesenchymal transition increase OPG production and secretion.•OPG induced endothelial cell migration and reactive oxygen species production.•OPG induced VIC proliferation and collagen production.•OPG plasma levels were highly increased in MVP patients than control subjects.