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二氢吴茱萸碱通过 Wnt7b/CCND1 轴抑制血管重构。

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis.

机构信息

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.

Drug Clinical Trial Institution, the Affiliated Hospital of Zunyi Medical University, Zunyi, China.

出版信息

J Cardiovasc Pharmacol. 2022 Jul 1;80(1):48-55. doi: 10.1097/FJC.0000000000001239.

DOI:10.1097/FJC.0000000000001239
PMID:35170494
Abstract

Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

摘要

血管成形术常因血管平滑肌细胞(VSMC)的异常增殖而失败。如果给予一种能有效改善异常血管重塑的药物,血管成形术的成功率可能会提高。淫羊藿次苷 II(ICS-II)是一种从中药淫羊藿中提取的天然黄酮醇糖苷,具有多种对人类有益的药用特性。然而,ICS-II 对异常血管重塑的作用尚未阐明。本研究旨在体内研究 ICS-Ⅱ对大鼠球囊损伤性内膜增生的分子作用,以及在原代大鼠主动脉平滑肌细胞(VSMC)中对血小板衍生生长因子诱导的血管增殖的作用。ICS-II 与本研究中的阳性对照雷帕霉素一样有效。ICS-II 抑制损伤大鼠颈总动脉的新生内膜形成,并显著降低 Wnt7b 的表达。ICS-Ⅱ显著抑制血小板衍生生长因子诱导的 VSMC 增殖。细胞周期分析表明,ICS-II 在 G1/S 转换过程中触发细胞周期停滞。Western blot 分析进一步表明,这种细胞周期停滞可能是通过抑制 Wnt7b 导致 CCND1 抑制。总之,我们的研究结果表明,ICS-II 具有显著的抗增殖特性,可拮抗异常血管新生内膜增生。这种现象很可能是由于抑制了 Wnt7b/CCND1 轴。

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