Orr Anthony Wayne, Hastings Nicole E, Blackman Brett R, Wamhoff Brian R
Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, La., USA.
J Vasc Res. 2010;47(2):168-80. doi: 10.1159/000250095. Epub 2009 Oct 22.
Vascular smooth muscle cell (SMC) phenotypic modulation plays a key role in atherosclerosis and is classically defined as a switch from a 'contractile' phenotype to a 'synthetic' phenotype, whereby genes that define the contractile SMC phenotype are suppressed and proliferation and/or migratory mechanisms are induced. There is also evidence that SMCs may take on a 'proinflammatory' phenotype, whereby SMCs secrete cytokines and express cell adhesion molecules, e.g. IL-8, IL-6, and VCAM-1, respectively, which may functionally regulate monocyte and macrophage adhesion and other processes during atherosclerosis. Factors that drive the inflammatory phenotype are not limited to cytokines but also include hemodynamic forces imposed on the blood vessel wall and intimate interaction of endothelial cells with SMCs, as well as changes in matrix composition in the vessel wall. However, it is critical to recognize that our understanding of the complex interaction of these multiple signal inputs has only recently begun to shed light on mechanisms that regulate the inflammatory SMC phenotype, primarily through models that attempt to recreate this environment ex vivo. The goal of this review is to summarize our current knowledge in this area and identify some of the key unresolved challenges and questions requiring further study.
血管平滑肌细胞（SMC）表型调节在动脉粥样硬化中起关键作用，传统上被定义为从“收缩性”表型向“合成性”表型的转变，即定义收缩性SMC表型的基因被抑制，增殖和/或迁移机制被诱导。也有证据表明，SMC可能呈现“促炎”表型，即SMC分别分泌细胞因子并表达细胞黏附分子，如IL-8、IL-6和VCAM-1，这些分子可能在功能上调节动脉粥样硬化过程中的单核细胞和巨噬细胞黏附及其他过程。驱动炎症表型的因素不仅限于细胞因子，还包括施加在血管壁上的血流动力学力、内皮细胞与SMC的密切相互作用，以及血管壁基质组成的变化。然而，至关重要的是要认识到，我们对这些多种信号输入复杂相互作用的理解直到最近才开始揭示调节炎症性SMC表型的机制，主要是通过试图在体外重现这种环境的模型。本综述的目的是总结我们目前在该领域的知识，并确定一些关键的未解决挑战和需要进一步研究的问题。
