Ge Xie, Chen Siyu, Liu Mei, Liang Tingming, Liu Chang
Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Int J Mol Sci. 2015 Nov 26;16(12):28180-93. doi: 10.3390/ijms161226093.
The uncontrolled migration of vascular smooth muscle cells (VSMCs) into the intima is a critical process in the development of atherosclerosis. Evodiamine, an indole alkaloid extracted from the Chinese medicine evodia, has been shown to inhibit tumor cell invasion and protect the cardiovascular system, but its effects on VSMCs remain unknown. In the present study, we investigated the inhibitory effects of evodiamine on the platelet-derived growth factor-BB (PDGF-BB)-induced VSMC migration using wound healing and transwell assays, and assessed its role in decreasing the protein levels of matrix metalloproteinases and cell adhesion molecules. More importantly, we found that evodiamine activated the expression and nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ). Inhibition of PPARγ activity by using its antagonist T0070907 and its specific siRNA oligonucleotides significantly attenuated the inhibitory effects of evodiamine on VSMC migration. Taken together, our results indicate a promising anti-atherogenic effect of evodiamine through attenuation of VSMC migration by activating PPARγ.
血管平滑肌细胞（VSMCs）不受控制地迁移到内膜是动脉粥样硬化发展过程中的一个关键过程。吴茱萸碱是从中药吴茱萸中提取的一种吲哚生物碱，已被证明能抑制肿瘤细胞侵袭并保护心血管系统，但其对血管平滑肌细胞的作用尚不清楚。在本研究中，我们使用伤口愈合实验和Transwell实验研究了吴茱萸碱对血小板衍生生长因子-BB（PDGF-BB）诱导的血管平滑肌细胞迁移的抑制作用，并评估了其在降低基质金属蛋白酶和细胞粘附分子蛋白水平方面的作用。更重要的是，我们发现吴茱萸碱激活了过氧化物酶体增殖物激活受体γ（PPARγ）的表达和核转位。使用其拮抗剂T0070907及其特异性siRNA寡核苷酸抑制PPARγ活性，显著减弱了吴茱萸碱对血管平滑肌细胞迁移的抑制作用。综上所述，我们的结果表明，吴茱萸碱通过激活PPARγ减弱血管平滑肌细胞迁移，具有潜在的抗动脉粥样硬化作用。
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