McIntosh Chelsea T, Warnock James N
Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi, 39762, USA.
J Heart Valve Dis. 2013 Sep;22(5):631-9.
Aortic valve ectopic calcification occurs exclusively on the fibrosa surface. This may be due to the distinct mechanical environments on either side of the valve, or to the existence of unique, side-specific endothelial sub-phenotypes. The study aim was to determine if side-specific endothelial cells (ECs) would differentially express cell-cell and cell-matrix adhesion molecules in response to elevated levels of equibiaxial tensile strain.
Side-specific porcine aortic valve ECs were isolated and strained at 10% or 20% using a Flexcell 4000T for 24 h, and compared to static controls. The quantity and pattern of distribution of adhesion proteins was then assessed using ELISA and fluorescence microscopy, respectively. The adhesion proteins of interest were platelet endothelial cell adhesion molecule-1 (PECAM-1), beta1-integrin, VE-cadherin, and vinculin.
Overall, ventricular ECs were more reactive to changes in cyclic strain, with significant increases in VE-cadherin and vinculin at 20% strain. However, the expression of beta1-integrin was significantly increased at 20% strain in fibrosa ECs. Expression of PECAM-1 was not significantly changed at all strain levels for both sub-populations of ECs.
Endothelial cells isolated from the fibrosa and ventricularis surfaces of porcine aortic valves showed significantly different expression profiles of cell-cell and cell-extracellular matrix adhesion molecules under elevated tensile strain. These differences in response to cyclic strain suggest that different endothelial sub-phenotypes exist on the fibrosa and ventricularis surfaces of the aortic valve.
主动脉瓣异位钙化仅发生在纤维层表面。这可能是由于瓣膜两侧不同的力学环境,或者是由于存在独特的、特定侧的内皮亚表型。本研究的目的是确定特定侧的内皮细胞(ECs)在等双轴拉伸应变水平升高时是否会差异表达细胞间和细胞与基质的黏附分子。
分离猪主动脉瓣特定侧的内皮细胞,使用Flexcell 4000T以10%或20%的应变拉伸24小时,并与静态对照进行比较。然后分别使用酶联免疫吸附测定(ELISA)和荧光显微镜评估黏附蛋白的数量和分布模式。感兴趣的黏附蛋白是血小板内皮细胞黏附分子-1(PECAM-1)、β1整合素、血管内皮钙黏蛋白(VE-钙黏蛋白)和纽蛋白。
总体而言,心室侧内皮细胞对周期性应变变化的反应更强,在20%应变时VE-钙黏蛋白和纽蛋白显著增加。然而,在20%应变时,纤维层内皮细胞中β1整合素的表达显著增加。对于两个内皮细胞亚群,在所有应变水平下PECAM-1的表达均无显著变化。
从猪主动脉瓣纤维层和心室层表面分离的内皮细胞在拉伸应变升高时,细胞间和细胞与细胞外基质黏附分子的表达谱存在显著差异。对周期性应变的这些差异反应表明,主动脉瓣纤维层和心室层表面存在不同的内皮亚表型。