Metformin attenuates carotid neointimal hyperplasia by modulating the vascular smooth muscle cell phenotype transformation through upregulation of TET2, Nur77 and calponin

IF 0.7 4区生物学 Q4 BIOLOGY

Archives of Biological Sciences Pub Date : 2021-01-01 DOI:10.2298/ABS201103009L

H. Lin, Shuo Cheng, Zhichao Yuan, Zhiqiang Yan, Jifa Zhang

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引用次数: 0

Abstract

Metformin is a drug used to treat type 2 diabetes based on its effectiveness as well as cardiovascular safety. Metformin has been shown to modulate proliferation and migration of vascular smooth muscle cells (VSMCs), but the underlying mechanisms of the effect of metformin on VSMC function remains unclear. We found that metformin inhibits VSMC proliferation and migration and upregulates the expression of nuclear receptor subfamily 4 group A member 1 (Nur77), ten-eleven translocation 2 (TET2), and calponin in vitro. In the carotid artery balloon injury model of rats, metformin effectively prevented neointimal hyperplasia in the carotid artery, including neointimal thickness, increased neointimal area, and the neointimal area/medial area ratio. It also reduced the number of proliferating cell nuclear antigen (PCNA)+ cells and increased the expression of Nur77, calponin and alpha-smooth muscle actin (?-SMA). These results show that metformin attenuates neointimal hyperplasia in balloon-injured carotid arteries via increased expression of TET2, Nur77 and calponin, and reduced expression of matrix metallopeptidase 9 (MMP-9).

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二甲双胍通过上调TET2、Nur77和钙钙蛋白，调节血管平滑肌细胞表型转化，减轻颈动脉内膜增生

二甲双胍是一种用于治疗2型糖尿病的药物，基于其有效性和心血管安全性。二甲双胍已被证明可以调节血管平滑肌细胞(VSMC)的增殖和迁移，但二甲双胍影响VSMC功能的潜在机制尚不清楚。我们发现二甲双胍在体外抑制VSMC增殖和迁移，并上调核受体亚家族4 A组成员1 (Nur77)、10 - 11易位2 (TET2)和钙钙蛋白的表达。在大鼠颈动脉球囊损伤模型中，二甲双胍能有效地阻止颈动脉内膜增生，包括内膜厚度、内膜面积增加、内膜面积/内侧面积比值。减少增殖细胞核抗原(PCNA)+细胞的数量，增加Nur77、calponin和α -平滑肌肌动蛋白(?-SMA)的表达。这些结果表明，二甲双胍通过增加TET2、Nur77和钙钙蛋白的表达，降低基质金属肽酶9 (MMP-9)的表达，减轻了球囊损伤的颈动脉内膜增生。

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来源期刊

Archives of Biological Sciences 生物-生物学

CiteScore

1.40

自引率

0.00%

发文量

审稿时长

3-8 weeks

期刊介绍： The Archives of Biological Sciences is a multidisciplinary journal that covers original research in a wide range of subjects in life science, including biology, ecology, human biology and biomedical research. The Archives of Biological Sciences features articles in genetics, botany and zoology (including higher and lower terrestrial and aquatic plants and animals, prokaryote biology, algology, mycology, entomology, etc.); biological systematics; evolution; biochemistry, molecular and cell biology, including all aspects of normal cell functioning, from embryonic to differentiated tissues and in different pathological states; physiology, including chronobiology, thermal biology, cryobiology; radiobiology; neurobiology; immunology, including human immunology; human biology, including the biological basis of specific human pathologies and disease management.