Shojaei Shahrokh, Tafazzoli-Shahdpour Mohammad, Shokrgozar Mohammad Ali, Haghighipour Nooshin
Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
Cell Biol Int. 2015 Jun;39(6):741-9. doi: 10.1002/cbin.10443. Epub 2015 Jan 28.
It has been well established that biomechanical environment can influence functionality of biological cells. There are evidences that show mechanical cyclic stretch can promote smooth muscle cell (SMC) markers in endothelial cells (ECs). The objective of this study was to determine whether mechanical stimuli in the forms of uniaxial and equiaxial cyclic stretches (UNCS and EQCS) can affect endothelial and smooth muscle gene expressions in mRNA level of human umbilical vein endothelial cells (HUVECs). For this purpose, 10% uniaxial UNCS and EQCS (60 cycles/min for 24 h) were applied on HUVECs, and using real-time PCR expressions of three EC specific markers, vascular endothelial growth factor receptor-2 (VEGFR-2, also known as FLK-1), von Willebrand Factor (vWF) and vascular endothelial-cadherin (VE-cadherin) and two SMC specific genes, α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SMMHC) were quantified. Moreover, alterations in cell height were analyzed by atomic force microscopy (AFM). Results showed that cyclic UNCS for 24 h downregulated the expression of all EC markers and upregulated the expression of all SMC markers while low effects on HUVECs height were observed. Cyclic EQCS in the same conditions resulted in minor effect on SMC gene expression in HUVECs, while led to strong reduction in vWF with no significant change in other two endothelial genes. Cyclic EQCS considerably elevated cell height. Results proposed that ECs can transdifferentiate to SMC phenotype under specific microenvironmental conditions.
生物力学环境能够影响生物细胞的功能，这一点已经得到了充分证实。有证据表明，机械循环拉伸能够促进内皮细胞（ECs）中平滑肌细胞（SMC）标志物的表达。本研究的目的是确定单轴和等轴循环拉伸（UNCS和EQCS）形式的机械刺激是否会影响人脐静脉内皮细胞（HUVECs）mRNA水平上的内皮和平滑肌基因表达。为此，对HUVECs施加10%的单轴UNCS和EQCS（60次/分钟，持续24小时），并使用实时PCR对三种EC特异性标志物血管内皮生长因子受体-2（VEGFR-2，也称为FLK-1）、血管性血友病因子（vWF）和血管内皮钙黏蛋白（VE-钙黏蛋白）以及两种SMC特异性基因α-平滑肌肌动蛋白（α-SMA）和平滑肌肌球蛋白重链（SMMHC）的表达进行定量分析。此外，通过原子力显微镜（AFM）分析细胞高度的变化。结果显示，24小时的循环UNCS下调了所有EC标志物的表达，上调了所有SMC标志物的表达，同时观察到对HUVECs高度的影响较小。相同条件下的循环EQCS对HUVECs中SMC基因表达的影响较小，而导致vWF显著降低，其他两种内皮基因无显著变化。循环EQCS显著提高了细胞高度。结果表明，在特定的微环境条件下，ECs可以转分化为SMC表型。
