The effects of combined cyclic stretch and pressure on the aortic valve interstitial cell phenotype.
The effects of combined cyclic stretch and pressure on the aortic valve interstitial cell phenotype.
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DOI：
10.1007/s10439-011-0273-x
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发表时间：
2011-06
影响因子：
3.8
通讯作者：
Yoganathan AP
中科院分区：
文献类型：
--
作者：
Thayer P;Balachandran K;Rathan S;Yap CH;Arjunon S;Jo H;Yoganathan AP
主动脉瓣间质细胞（VIC）可以表现出成纤维细胞、肌成纤维细胞和平滑肌细胞的表型特征。其他人提出，在疾病发生和进展过程中，瓣膜细胞被激活并表现出肌成纤维细胞或成纤维细胞特征；然而，调节这种表型变化的线索仍不清楚。我们假设瓣膜所经历的机械力在调节瓣膜的天然表型中发挥作用，并且改变的机械力导致激活的表型。使用新型体外循环拉伸和压力生物反应器，我们将猪主动脉瓣（AV）小叶置于正常和病理性拉伸和压力大小的组合下。使用免疫组织化学和免疫印迹分析肌成纤维细胞标记物 α-SMA 和 Vimentin，以及平滑肌标记物 Calponin 和 Caldesmon。使用莫瓦特五色染色分析组织结构。我们报告说，病理性拉伸和压力抑制了收缩性，并可能抑制了肌成纤维细胞表型，如 α-SMA、Vimentin 和 Calponin 蛋白的下调所示。特别是，钙调蛋白下调意味着肌动蛋白丝解聚，并可能转化为更合成的（非收缩性）表型。这与在升高的压力和拉伸下观察到的海绵和纤维厚度的增加非常吻合，这通常表明基质合成增加。因此，我们的研究证明了循环拉伸和压力如何共同作用来调节 AVIC 表型。
Aortic valve interstitial cells (VIC) can exhibit phenotypic characteristics of fibroblasts, myofibroblasts, and smooth muscle cells. Others have proposed that valve cells become activated and exhibit myofibroblast or fibroblast characteristics during disease initiation and progression; however, the cues that modulate this phenotypic change remain unclear. We hypothesize that the mechanical forces experienced by the valve play a role in regulating the native phenotype of the valve and that altered mechanical forces result in an activated phenotype. Using a novel ex vivo cyclic stretch and pressure bioreactor, we subjected porcine aortic valve (AV) leaflets to combinations of normal and pathological stretch and pressure magnitudes. The myofibroblast markers α-SMA and Vimentin, along with the smooth muscle markers Calponin and Caldesmon, were analyzed using immunohistochemistry and immunoblotting. Tissue structure was analyzed using Movat’s pentachrome staining. We report that pathological stretch and pressure inhibited the contractile and possibly myofibroblast phenotypes as indicated by downregulation of the proteins α-SMA, Vimentin, and Calponin. In particular, Calponin downregulation implies depolymerization of actin filaments and possible conversion to a more synthetic (non-contractile) phenotype. This agreed well with the increase in spongiosa and fibrosa thickness observed under elevated pressure and stretch that are typically indicative of increased matrix synthesis. Our study therefore demonstrates how cyclic stretch and pressure may possibly act together to modulate the AVIC phenotype.