Hsu Steven, Chu Julia S, Chen Fanqing F, Wang Aijun, Li Song
Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Cell Mol Bioeng. 2011 Dec;4(4):627-636. doi: 10.1007/s12195-011-0205-8.
Vascular smooth muscle cells (SMCs) are a major cell type involved in vascular remodeling. The various developmental origins of SMCs such as neural crest and mesoderm result in heterogeneity of SMCs, which plays an important role in the development of vascular remodeling and diseases. Upon vascular injury, SMCs are exposed to blood flow and subjected to fluid shear stress. Previous studies have shown that fluid shear stress inhibits SMC proliferation. However, the effect of shear stress on the subpopulation of SMCs from specific developmental origin and vascular bed is not well understood. Here we investigated how shear stress regulates human aortic SMCs positive for neural crest markers. DNA microarray analysis showed that shear stress modulates the expression of genes involved in cell proliferation, matrix synthesis, cell signaling, transcription and cytoskeleton organization. Further studies demonstrated that shear stress induced SMC proliferation and cyclin D1, downregulated cell cycle inhibitor p21, and activated Akt pathway. Inhibition of PI-3 kinase blocked these shear stress-induced changes. These results suggest that SMCs with neural crest characteristics may respond to shear stress in a different manner. This finding has significant implications in the remodeling and diseases of blood vessels.
血管平滑肌细胞（SMCs）是参与血管重塑的主要细胞类型。SMCs的多种发育起源，如神经嵴和中胚层，导致了SMCs的异质性，这在血管重塑和疾病的发展中起着重要作用。血管损伤时，SMCs暴露于血流中并受到流体剪切应力作用。先前的研究表明，流体剪切应力可抑制SMCs增殖。然而，剪切应力对特定发育起源和血管床的SMCs亚群的影响尚不清楚。在此，我们研究了剪切应力如何调节神经嵴标志物阳性的人主动脉SMCs。DNA微阵列分析表明，剪切应力可调节参与细胞增殖、基质合成、细胞信号传导、转录和细胞骨架组织的基因表达。进一步研究表明，剪切应力诱导SMCs增殖和细胞周期蛋白D1表达，下调细胞周期抑制剂p21，并激活Akt信号通路。抑制PI-3激酶可阻断这些剪切应力诱导的变化。这些结果表明，具有神经嵴特征的SMCs可能以不同方式对剪切应力作出反应。这一发现对血管重塑和疾病具有重要意义。
