Mitral valve endothelial cells secrete osteoprotegerin during endothelial mesenchymal transition

作者：Songia Paola; Branchetti Emanuela; Parolari Alessandro; Myasoedova Veronika; Ferrari Giovanni; Alamanni Francesco; Tremoli Elena; Poggio Paolo

来源：Journal of Molecular and Cellular Cardiology, 2016, 98: 48-57.

DOI：10.1016/j.yjmcc.2016.06.061

• Circulating marker
• Endothelial to mesenchymal transition
• Mitral valve prolapse
• Valve endothelial cells
• Valve interstitial cells

Aims: 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.
Methods and results: 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.
Conclusion: 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.

• 出版日期2016-9