Kim Na Young, Kohn Julie C, Huynh John, Carey Shawn P, Mason Brooke N, Vouyouka Ageliki G, Reinhart-King Cynthia A
Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
Divison of Vascular Surgery at Mount Sinai Hospital, New York, New York, United States of America.
PLoS One. 2015 Mar 18;10(3):e0119008. doi: 10.1371/journal.pone.0119008. eCollection 2015.
Vascular smooth muscle cell (VSMC) migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP) secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu), however little is known about the physiological cues that drive podosome formation. We present the first evidence that physiological, physical stimuli mimicking cues present within the microenvironment of diseased arteries can induce podosome formation in VSMCs. Both microtopographical cues and imposed pressure mimicking stage II hypertension induce podosome formation in A7R5 rat aortic smooth muscle cells. Moreover, wounding using a scratch assay induces podosomes at the leading edge of VSMCs. Notably the effect of each of these biophysical stimuli on podosome stimulation can be inhibited using a Src inhibitor. Together, these data indicate that physical cues can induce podosome formation in VSMCs.
血管平滑肌细胞（VSMC）迁移和基质降解与动脉粥样硬化、血管损伤和再狭窄相关的内膜增生有关。一种提出的VSMCs降解基质的机制是通过使用足体，足体是基于肌动蛋白的瞬时结构，被认为通过产生基质金属蛋白酶（MMP）分泌的局部位点在细胞外基质降解中发挥作用。迄今为止，VSMCs中的足体主要通过用佛波酯刺激细胞来研究，如佛波醇12,13 - 二丁酸酯（PDBu），然而对于驱动足体形成的生理信号知之甚少。我们提供了首个证据，即模拟病变动脉微环境中存在的信号的生理、物理刺激可诱导VSMCs中足体的形成。微观地形信号和模拟II期高血压的施加压力均可诱导A7R5大鼠主动脉平滑肌细胞中足体的形成。此外，使用划痕试验造成创伤可在VSMCs的前沿诱导足体形成。值得注意的是，使用Src抑制剂可抑制这些生物物理刺激中的每一种对足体刺激的作用。总之，这些数据表明物理信号可诱导VSMCs中足体的形成。
