Songia Paola, Branchetti Emanuela, Parolari Alessandro, Myasoedova Veronika, Ferrari Giovanni, Alamanni Francesco, Tremoli Elena, Poggio Paolo
Centro Cardiologico Monzino IRCCS, Milan, Italy; Università degli Studi di Milano, Dipartimento di Scienze Farmacologiche e Biomolecolari, Milan, Italy.
University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA.
J Mol Cell Cardiol. 2016 Sep;98:48-57. doi: 10.1016/j.yjmcc.2016.06.061. Epub 2016 Jun 23.
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.
二尖瓣脱垂（MVP）在普通人群中的患病率为3%，全球受影响人数超过1.76亿。尽管如此，对于MVP进展所涉及的分子和细胞机制知之甚少，手术干预是唯一可用的选择。在本研究中，我们调查了骨保护素（OPG）在MVP的内皮向间充质转化（EndMT）过程中的作用。
从接受二尖瓣修复的患者（n = 25）的二尖瓣后叶分离出血管内皮细胞（VECs）和平滑肌细胞（VICs）。从57名受试者（29名对照者和28名MVP患者）中采集血浆。记录了EndMT过程中OPG的过表达及其以活性氧增加和迁移加速为特征的自分泌效应。此外，OPG增加了VIC的增殖。最后，与对照受试者相比，MVP患者的血浆OPG水平显著更高，ROC曲线下面积为0.92。
EndMT已被认为是MVP可能的病理机制。我们首次报道了OPG参与MVP分离细胞的细胞和分子变化。此外，与对照组相比，我们检测到MVP患者循环中OPG水平升高，这支持了OPG参与MVP发生和进展的假说。
