Extracellular Matrix Proteins and Substrate Stiffness Synergistically Regulate Vascular Smooth Muscle Cell Migration and Cortical Cytoskeleton Organization.
Extracellular Matrix Proteins and Substrate Stiffness Synergistically Regulate Vascular Smooth Muscle Cell Migration and Cortical Cytoskeleton Organization.
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DOI：
10.1021/acsabm.0c00100
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发表时间：
2020-04-20
影响因子：
4.7
通讯作者：
Hong Z
中科院分区：
文献类型：
--
作者：
Rickel AP;Sanyour HJ;Leyda NA;Hong Z
血管平滑肌细胞（VSMC）迁移是心血管疾病和衰老进展的关键步骤。迁移的VSMC遇到高度异质性的环境，由于不同区域中胶原蛋白和纤连蛋白（FN）的差异合成，细胞外基质（ECM）组成不同，硬度变化很大，从斑块的软坏死核心到血管壁内的硬钙化。在这项研究中，我们展示了一个应用程序的二维（2D）模型组成的弹性可调聚丙烯酰胺凝胶的不同刚度和ECM蛋白涂层研究VSMC迁移。该模型模拟了VSMC在血管壁内经历的体内微环境，这可能有助于确定治疗动脉粥样硬化的潜在治疗靶点。我们发现，基板刚度有不同的影响，对VSMC迁移1型胶原蛋白（COL1）和FN涂层基板。COL1涂层基板上的血管平滑肌细胞表现出显着减少的迁移距离较硬的基板上，而FN涂层基板上的血管平滑肌细胞有显着增加的迁移距离。此外，在更坚硬的COL 1涂层基底上培养的VSMC中，皮质应力纤维取向增加，而在更坚硬的FN涂层基底上培养的VSMC中，皮质应力纤维取向减少。在这两种蛋白质上，更无序的细胞骨架结构与更快的迁移相关。总体而言，这些结果表明，不同的ECM蛋白质可以导致底物硬度对心血管疾病和衰老进展中的VSMC迁移具有不同的影响。
Vascular smooth muscle cell (VSMC) migration is a critical step in the progression of cardiovascular disease and aging. Migrating VSMCs encounter a highly heterogeneous environment with the varying extracellular matrix (ECM) composition due to the differential synthesis of collagen and fibronectin (FN) in different regions and greatly changing stiffness, ranging from the soft necrotic core of plaques to hard calcifications within blood vessel walls. In this study, we demonstrate an application of a two-dimensional (2D) model consisting of an elastically tunable polyacrylamide gel of varying stiffness and ECM protein coating to study VSMC migration. This model mimics the in vivo microenvironment that VSMCs experience within a blood vessel wall, which may help identify potential therapeutic targets for the treatment of atherosclerosis. We found that substrate stiffness had differential effects on VSMC migration on type 1 collagen (COL1) and FN-coated substrates. VSMCs on COL1-coated substrates showed significantly diminished migration distance on stiffer substrates, while on FN-coated substrates VSMCs had significantly increased migration distance. In addition, cortical stress fiber orientation increased in VSMCs cultured on more rigid COL1-coated substrates, while decreasing on stiffer FN-coated substrates. On both proteins, a more disorganized cytoskeletal architecture was associated with faster migration. Overall, these results demonstrate that different ECM proteins can cause substrate stiffness to have differential effects on VSMC migration in the progression of cardiovascular diseases and aging.
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影响因子：
16.6
作者：
Bangasser BL;Shamsan GA;Chan CE;Opoku KN;Tüzel E;Schlichtmann BW;Kasim JA;Fuller BJ;McCullough BR;Rosenfeld SS;Odde DJ
通讯作者：
Odde DJ
影响因子：
5.8
作者：
Leskinen, MJ;Kovanen, PT;Lindstedt, KA
通讯作者：
Lindstedt, KA
DOI：
10.1073/pnas.1611324113
发表时间：
2016-10-04
影响因子：
11.1
作者：
Hartman, Christopher D.;Isenberg, Brett C.;Wong, Joyce Y.
通讯作者：
Wong, Joyce Y.
影响因子：
2.4
作者：
Akyildiz, Ali C.;Speelman, Lambert;Gijsen, Frank J. H.
通讯作者：
Gijsen, Frank J. H.
影响因子：
3.7
作者：
Hartman CD;Isenberg BC;Chua SG;Wong JY
通讯作者：
Wong JY