Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada.
J Biomech. 2012 Mar 15;45(5):882-7. doi: 10.1016/j.jbiomech.2011.11.030. Epub 2011 Dec 19.
Increasing evidence indicates that the progression of calcific aortic valve disease (CAVD) is influenced by the mechanical forces experienced by valvular interstitial cells (VICs) embedded within the valve matrix. The ability of VICs to sense and respond to tissue-level mechanical stimuli depends in part on cellular-level biomechanical properties, which may change with disease. In this study, we used micropipette aspiration to measure the instantaneous elastic modulus of normal VICs and of VICs induced to undergo pathological differentiation in vitro to osteoblast or myofibroblast lineages on compliant and stiff collagen gels, respectively. We found that VIC elastic modulus increased after subculturing on stiff tissue culture-treated polystyrene and with pathological differentiation on the collagen gels. Fibroblast, osteoblast, and myofibroblast VICs had distinct cellular-level elastic properties that were not fully explained by substrate stiffness, but were correlated with α-smooth muscle actin expression levels. C-type natriuretic peptide, a peptide expressed in aortic valves in vivo, prevented VIC stiffening in vitro, consistent with its ability to inhibit α-smooth muscle actin expression and VIC pathological differentiation. These data demonstrate that VIC phenotypic plasticity and mechanical adaptability are linked and regulated both biomechanically and biochemically, with the potential to influence the progression of CAVD.
越来越多的证据表明，心脏瓣膜间质细胞（VIC）在瓣膜基质中的机械力影响着心脏瓣膜钙化疾病（CAVD）的进展。VIC 感知和响应组织水平机械刺激的能力部分取决于细胞水平的生物力学特性，而这些特性可能会随着疾病的发展而发生变化。在这项研究中，我们使用微管吸吮技术来测量正常 VIC 和在体外诱导向成骨细胞或肌成纤维细胞谱系分化的 VIC 的瞬时弹性模量，分别在顺应性和刚性胶原蛋白凝胶上。我们发现，VIC 在刚性组织培养处理的聚苯乙烯上进行传代培养后以及在胶原蛋白凝胶上发生病理性分化后，弹性模量增加。成纤维细胞、成骨细胞和肌成纤维细胞的 VIC 具有不同的细胞水平弹性特性，这些特性不能完全用基质硬度来解释，但与α-平滑肌肌动蛋白表达水平相关。C 型利钠肽是一种在体内主动脉瓣中表达的肽，可防止 VIC 在体外变硬，这与其抑制α-平滑肌肌动蛋白表达和 VIC 病理性分化的能力一致。这些数据表明，VIC 的表型可塑性和机械适应性是相互联系的，并受到生物力学和生物化学的调节，这有可能影响 CAVD 的进展。
