Tetramethylpyrazine and paeoniflorin combination (TMP-PF) inhibits angiogenesis in atherosclerosis via miR-126/VEGF/VEGFR2 signaling pathway

血管生成 川芎嗪 化学 脐静脉 癌症研究 辛伐他汀 血管内皮生长因子 分子生物学 药理学 生物化学 生物 医学 血管内皮生长因子受体 病理 体外 替代医学
作者
Yongsheng Yuan,Rong Yuan,Qiqi Xin,Miao Yu,Ying Chen,Rui Gao,Weihong Cong
出处
期刊:Journal of future foods [Elsevier]
卷期号:4 (3): 280-287
标识
DOI:10.1016/j.jfutfo.2023.07.010
摘要

Angiogenesis in atherosclerosis (AS) promotes plaque destabilization. miR-126 has a significant role in angiogenesis. Tetramethylpyrazine (TMP) and paeoniflorin (PF) have anti-atherosclerotic effects. However, the miR-126-related mechanisms of TMP and PF combination (TMP-PF) on angiogenesis in AS have not been understood. To explore the mechanism of TMP-PF on angiogenesis in AS targeting miR-126. Human umbilical vein endothelial cells (HUVECs) were assigned into the control, model, TMP-PF, TMP-PF + miR-126 inhibitor, and simvastatin groups. HUVECs were transfected with miR-126 inhibitor or negative control, incubated with oxidized low-density lipoprotein (ox-LDL) to establish AS model, and then treated with TMP-PF or simvastatin. Cell proliferation, migration, and tube formation assays are conducted, and the expression of angiogenesis-related factors were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The expression level of miR-126 was confirmed by polymerase chain reaction (PCR). ox-LDL promoted HUVECs proliferation, migration, and tube formation, downregulated miR-126 expression, and increased the expression of VEGF, VEGFR2, bFGF, and FGFR1. TMP-PF inhibited proliferation, migration, and tube formation, upregulated miR-126 expression and decreased the expression of VEGF, VEGFR2, bFGF, and FGFR1 in ox-LDL-induced HUVECs. However, the effects of TMP-PF on angiogenesis and the expression of miR-126, VEGF, VEGFR2, and FGFR1 were abolished by miR-126 inhibitor. TMP-PF suppressed angiogenesis in AS by regulating miR-126/VEGF/VEGFR2 pathway, which might elucidate the underlying mechanism of TMP-PF in alleviating AS.
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