Stephens Elizabeth H, Durst Christopher A, Swanson Julia C, Grande-Allen K Jane, Ingels Neil B, Miller D Craig
Department of Bioengineering, Rice University, Houston, TX.
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA.
Cell Mol Bioeng. 2010 Dec;3(4):428-437. doi: 10.1007/s12195-010-0139-6. Epub 2010 Aug 25.
Once considered passive flaps, we now understand that mitral leaflets are dynamic structures with their own vasculature and innervation that actively remodel and even generate force in response to their environments. Valvular interstitial cells (VICs) are contractile and could underlie mitral leaflet force generation, but the exact mechanisms for VICs in mitral leaflet force generation are not understood. This study tested the hypothesis that actin-mediated VIC force generation coupled to collagen via alphabeta integrins is necessary for force generation in the mitral leaflet. High magnification fluorescent imaging of freshly excised porcine mitral leaflets revealed VIC cytoplasm tightly conforming to collagen fibers, with actin within VIC cytoplasmic processes appearing to attach to the collagen fibers. Functional studies of isometric force development demonstrated that while control samples developed force in response to KCl, either blocking alphabeta integrins or blocking actin polymerization via cytochalasin abolished KCl-induced force development (p<0.001). These results strongly suggest that VIC-collagen coupling, mediated by alphabeta integrins, is necessary for KCl-induced force generation in the mitral leaflet. This functional coupling between collagen and VICs via alphabeta integrins may play a role for mitral valve function.
二尖瓣叶曾经被认为是被动瓣叶，而我们现在明白，二尖瓣叶是具有自身脉管系统和神经支配的动态结构，它们会根据周围环境积极重塑甚至产生力量。瓣膜间质细胞（VICs）具有收缩性，可能是二尖瓣叶产生力量的基础，但VICs在二尖瓣叶力量产生的确切机制尚不清楚。本研究检验了以下假设：通过αβ整合素与胶原蛋白耦合的肌动蛋白介导的VIC力量产生，对于二尖瓣叶的力量产生是必要的。对新鲜切除的猪二尖瓣叶进行高倍荧光成像显示，VIC细胞质紧密贴合胶原纤维，VIC细胞质突起内的肌动蛋白似乎附着于胶原纤维。等长力量发展的功能研究表明，虽然对照样本对氯化钾有力量反应，但阻断αβ整合素或通过细胞松弛素阻断肌动蛋白聚合，均消除了氯化钾诱导的力量发展（p<0.001）。这些结果强烈表明，由αβ整合素介导的VIC-胶原耦合，对于二尖瓣叶中氯化钾诱导的力量产生是必要的。通过αβ整合素在胶原蛋白和VICs之间的这种功能耦合，可能对二尖瓣功能起作用。
