"Obese" smooth muscle cells fail to assemble collagen fibrils.
"Obese" smooth muscle cells fail to assemble collagen fibrils.
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“肥胖”的平滑肌细胞无法组装胶原纤维。
DOI：
10.1161/circresaha.109.196337
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发表时间：
2009
影响因子：
20.1
通讯作者：
Leitinger,Norbert
中科院分区：
文献类型：
--
作者：
Leitinger,Norbert
平滑肌细胞在动脉粥样硬化斑块的稳定中起着重要作用。它们通过合成和组装纤维状胶原蛋白I来形成牢固的纤维帽，这是一个需要合成纤连蛋白和激活整合素的过程。然而，在动脉粥样硬化斑块形成过程中，细胞外基质成分发生变化。I型和III型胶原在健康血管壁中占主导地位，而在动脉粥样硬化形成期间，纤连蛋白和VIII型胶原由血管SMC合成。在晚期斑块中，SMC和巨噬细胞合成基质金属蛋白酶，降解基质蛋白，从而削弱纤维帽。在病变发展过程中，SMC表型从“收缩”表型变为“合成”表型。2已经表明，炎症介质和氧化磷脂诱导SMC的表型转换，因此也调节基质金属蛋白酶和胶原蛋白的产生。3决定迁移和增殖的SMC表型也控制基质合成和降解。4单体I型胶原蛋白是I型胶原蛋白分解的副产物，已显示进一步增强炎性SMC表型，5可能加剧胶原蛋白周转过程。此外，诱导平滑肌细胞凋亡导致细胞减少，从而增强动脉粥样硬化斑块的脆弱性。总之，认为基质蛋白如胶原和纤连蛋白的产生和组装减少以及降解增加的不平衡导致动脉粥样硬化纤维帽变薄并因此不稳定。6
Smooth muscle cells (SMCs) play an important role in the stabilization of atherosclerotic plaques. They contribute to form a firm fibrous cap by synthesizing and assembling fibrillar collagen I, a process that requires the synthesis of fibronectin and activation of integrins. However, extracellular matrix composition changes during the formation of atherosclerotic plaques. Type I and III collagens predominate in the healthy vessel wall, whereas during atherogenesis, fibronectin and type VIII collagen are synthesized by vascular SMCs. 1 In advanced plaques, SMCs and macrophages synthesize matrix metalloproteinases which degrade matrix proteins, thereby weakening the fibrous cap. During lesion development, SMC phenotypes change from a “contractile” to a “synthetic” phenotype. 2 It has been shown that inflammatory mediators and oxidized phospholipids induce phenotypic switching in SMCs and consequently also modulate matrix metalloproteinases and collagen production. 3 The SMC phenotype that determines migration and proliferation also controls matrix synthesis and degradation. 4 Monomeric type I collagen, a byproduct of collagen I breakdown, has been shown to further potentiate an inflammatory SMC phenotype, 5 possibly exacerbating the process of collagen turnover. Moreover, induction of apoptosis in SMCs results in decreased cellularity and thus enhanced vulnerability of atherosclerotic plaques. In summary, imbalance toward decreased production and assembly and increased degradation of matrix proteins such as collagens and fibronectin is believed to result in thinning and thus destabilization of the atherosclerotic fibrous cap. 6