miR-21对动脉粥样硬化血管平滑肌细胞生长的影响

Effect of miR-21 on the Growth of Atherosclerotic Vascular Smooth Muscle Cells

探究动脉粥样硬化(AS)患者中的miR-21表达水平并确定其潜在机制,分析miR-21对动脉粥样硬化血管平滑肌细胞生长的影响。通过逆转录定量PCR(RT-qPCR)检测AS患者的血液和血管斑块组织中的miR-21表达水平。当miR-21在人血管平滑肌细胞(h VSMCs)中上调和下调后,分析其在h VSMCs中的主要作用。分别使用Cell Counting kit-8测定法和流式细胞仪确定细胞增殖和凋亡的情况,结果显示AS患者的血液和血管斑块组织中的miR-21表达下调。基质金属肽酶-2(MMP-2)被证明是miR-21的直接靶基因,在AS患者的血液和血管斑块组织中被上调。此外,在h VSMC中,MMP-2被miR-21负调控,且在MMP-2下调和miR-21模拟物转染后,观察到h VSMC增殖的显著抑制和细胞凋亡的诱导。MMP-2过度表达可逆转miR-21模拟物对h VSMC增殖和凋亡的影响。试验证明,miR-21在AS中被下调,这将导致h VSMC细胞增殖受到抑制,并通过MMP-2诱导细胞凋亡。

To explore the expression level of miR-21 in patients with atherosclerosis( AS),to determine its underlying mechanism,and to analyze the effect of miR-21 on the growth of atherosclerotic vascular smooth muscle cells,the expression level of miR-21 in blood and vascular plaque of as patients was detected by RT-qPCR. The role of miR-21 in human vascular smooth muscle cells( h VSMCs) was studied after up and down regulation of miR-21 in h VSMCs. Cell counting kit-8 and flow cytometry was used to determine cell proliferation and apoptosis. The expression of miR-21 was down regulated in blood and vascular plaque of as patients.Matrix metallopeptidase-2( MMP-2) was proved to be the direct target gene of miR-21,which was up-regulated in blood and vascular plaque tissue of as patients. In addition,MMP-2 was negatively regulated by miR-21 in h VSMC. In addition,after down-regulation of MMP-2 and transfection of miR-21,significant inhibition of h VSMC proliferation and induction of apoptosis were observed. MMP-2 over-expression could reverse the effect of miR-21 on the proliferation and apoptosis of h VSMC. In general,miR-21 was down regulated,which led to the inhibition of h VSMC proliferation and apoptosis induced by MMP-2.