Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: implications for atherosclerosis.
Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: implications for atherosclerosis.
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DOI：
10.1002/jcp.22202
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发表时间：
2010-10
影响因子：
5.6
通讯作者：
Wong, Joyce Y.
中科院分区：
文献类型：
--
作者：
Brown, Xin Q.;Bartolak-Suki, Erzsebet;Williams, Corin;Walker, Mathew L.;Weaver, Valerie M.;Wong, Joyce Y.
血管疾病，如动脉粥样硬化，伴随着血管壁机械性能的变化。尽管机械结构改变被认为有助于疾病的进展，但血管壁僵硬促进血管闭塞性疾病的分子机制仍不清楚。众所周知，血小板衍生生长因子(PDGF)是血管平滑肌细胞(VSMCs)异常迁移和增殖的主要刺激因子，在血管疾病中起重要作用。在这里，我们使用机械性能可调的工程化基质来探索组织僵硬对VSMCs中PDGF信号的影响，以此作为血管壁硬化促进血管疾病的潜在机制。我们发现底物硬度显著增强了PDGFR活性和VSMC的增殖。在与配体结合后，PDGFR在刚性底物和软性底物上培养的细胞中遵循不同的激活途径，表现为其激活强度和激活时间、对胆固醇萃取剂的敏感性以及质膜定位的差异。我们的结果表明，血管壁僵硬可能通过增强PDGFR信号来促进VSMC的生长和存活，从而积极地促进血管疾病的发生。
Vascular disease, such as atherosclerosis, is accompanied by changes in the mechanical properties of the vessel wall. Although altered mechanics is thought to contribute to disease progression, the molecular mechanisms whereby vessel wall stiffening could promote vascular occlusive disease remain unclear. It is well known that platelet-derived growth factor (PDGF) is a major stimulus for the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) and contributes critically to vascular disease. Here we used engineered substrates with tunable mechanical properties to explore the effect of tissue stiffness on PDGF signaling in VSMCs as a potential mechanism whereby vessel wall stiffening could promote vascular disease. We found that substrate stiffness significantly enhanced PDGFR activity and VSMC proliferation. After ligand binding, PDGFR followed distinct routes of activation in cells cultured on stiff versus soft substrates, as demonstrated by differences in its intensity and duration of activation, sensitivity to cholesterol extracting agent, and plasma membrane localization. Our results suggest that stiffening of the vessel wall could actively promote pathogenesis of vascular disease by enhancing PDGFR signaling to drive VSMC growth and survival.
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影响因子：
4.9
作者：
Jacot, Jeffrey G.;Dianis, Scott;Wong, Joyce Y.
通讯作者：
Wong, Joyce Y.
影响因子：
7.8
作者：
Gaus, Katharina;Le Lay, Soazig;Balasubramanian, Nagaraj;Schwartz, Martin A
通讯作者：
Schwartz, Martin A
影响因子：
4.8
作者：
Arcaro, Alexandre;Aubert, Muriel;Seckl, Michael J.
通讯作者：
Seckl, Michael J.
影响因子：
5.3
作者：
Decker, L;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D