Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA/ROCK-dependent mechanism
Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA/ROCK-dependent mechanism
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DOI：
10.1016/j.yjmcc.2013.12.009
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发表时间：
2014-02-01
影响因子：
5
通讯作者：
Mathieu, Patrick
中科院分区：
文献类型：
--
作者：
Bouchareb, Rihab;Boulanger, Marie-Chloe;Mathieu, Patrick
钙化性主动脉瓣疾病（CAVD）是一种以瓣叶异常矿化为特征的慢性疾病，在二叶式主动脉瓣（BAV）中加速。怀疑机械应变可能促进/增强主动脉瓣的矿化。然而，在主动脉瓣矿化过程中，机械应变的影响和相关途径在很大程度上仍然未知。分离瓣膜间质细胞（VIC），并在应变条件下进行研究。人二叶式主动脉瓣作为增加机械应变的相关模型进行了检查。循环应变增加矿化的VIC的几倍。扫描电子显微镜（SEM）和能量色散X射线（EDX）分析表明，机械应变促进形成矿化的球状体微粒，合并成较大的结构在凋亡VIC的表面。细胞凋亡和矿化与ENPP 1的表达密切相关。ENPP 1的抑制大大降低了维克培养物的矿化。通过几个方面的证据，我们表明，机械应变促进出口ENPP 1含有囊泡的质膜通过RhoA/ROCK途径。在人BAV中进行的研究揭示了在高机械应变区域中存在球状矿化结构沿着ENPP 1的表达。机械应变促进VIC产生和积聚球状矿化微粒，这可能是参与主动脉瓣矿化的重要机制之一。RhoA/ROCK介导的ENPP 1向质膜的输出促进应变诱导的VIC矿化(C)2013爱思唯尔有限公司保留所有权利。
Calcific aortic valve disease (CAVD) is a chronic disorder characterized by an abnormal mineralization of the leaflets, which is accelerated in bicuspid aortic valve (BAV). It is suspected that mechanical strain may promote/enhance mineralization of the aortic valve. However, the effect of mechanical strain and the involved pathways during mineralization of the aortic valve remains largely unknown. Valve interstitial cells (VICs) were isolated and studied under strain conditions. Human bicuspid aortic valves were examined as a model relevant to increase mechanical strain. Cyclic strain increased mineralization of VICs by several-fold. Scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analyses revealed that mechanical strain promoted the formation of mineralized spheroid microparticles, which coalesced into larger structure at the surface of apoptotic VICs. Apoptosis and mineralization were closely associated with expression of ENPP1. Inhibition of ENPP1 greatly reduced mineralization of VIC cultures. Through several lines of evidence we showed that mechanical strain promoted the export of ENPP1-containing vesicles to the plasma membrane through a RhoA/ROCK pathway. Studies conducted in human BAV revealed the presence of spheroid mineralized structures along with the expression of ENPP1 in areas of high mechanical strain. Mechanical strain promotes the production and accumulation of spheroid mineralized microparticles by VICs, which may represent one important underlying mechanism involved in aortic valve mineralization. RhoA/ROCK-mediated export of ENPP1 to the plasma membrane promotes straininduced mineralization of VICs. (C) 2013 Elsevier Ltd. All rights reserved.