Cirka Heather A, Kural Mehmet H, Billiar Kristen L
Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, 01609.
J Long Term Eff Med Implants. 2015;25(1-2):3-16. doi: 10.1615/jlongtermeffmedimplants.2015011759.
Valvular interstitial cells (VICs) are the major cell type within aortic valve leaflets. VICs are able to exhibit a spectrum of phenotype characteristics including those of fibroblasts, smooth muscle cells, and myofibroblasts. VICs are responsible for valve maintenance and repair, yet excessive persistence of the myofibroblast phenotype is implicated in a number of valve diseases, including calcific aortic valve disease and fibrosis. Despite the prevalence of these diseases, the stimuli regulating the transition to the activated myofibroblast state and reversal to quiescent fibroblast and/or induction of apoptosis are not fully understood. The purpose of this article is to review in vitro studies that have contributed to the current understanding of mechanical regulation of VIC phenotype and fate. In particular, we have focused on studies utilizing advanced in vitro systems that allow modulation and measurement of cell tension and cell-generated forces in two-dimensional and three-dimensional cultures. In addition, we discuss the importance of cell tension in phenotype modulation and how cytoskeletal tension may contribute to aggregation and calcification. Future directions of pharmaceutical development aimed at reducing VIC cytoskeletal tension are also highlighted.
瓣膜间质细胞（VICs）是主动脉瓣叶内的主要细胞类型。VICs能够表现出一系列表型特征，包括成纤维细胞、平滑肌细胞和肌成纤维细胞的特征。VICs负责瓣膜的维持和修复，但肌成纤维细胞表型的过度持续与多种瓣膜疾病有关，包括钙化性主动脉瓣疾病和纤维化。尽管这些疾病很常见，但调节向活化肌成纤维细胞状态转变以及逆转至静止成纤维细胞和/或诱导细胞凋亡的刺激因素尚未完全明确。本文的目的是综述有助于当前对VIC表型和命运的机械调节理解的体外研究。特别是，我们重点关注了利用先进体外系统的研究，这些系统能够在二维和三维培养中调节和测量细胞张力以及细胞产生的力。此外，我们讨论了细胞张力在表型调节中的重要性，以及细胞骨架张力如何可能导致聚集和钙化。还强调了旨在降低VIC细胞骨架张力的药物开发的未来方向。
