Pan Chun-Hsu, Lin Yu-Pei, Wang Jie-Yu, Huang Hui-Yu, Huang Shun-Cheng, Lo Ji-Mehng, Wu Chieh-Hsi
Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
Evid Based Complement Alternat Med. 2021 Jun 30;2021:8466543. doi: 10.1155/2021/8466543. eCollection 2021.
Balloon angioplasty-induced neointimal hyperplasia remains a clinical problem that must be resolved. The bioactivities of the extract (CCE) have demonstrated potential in preventing the progression of restenosis. The present study evaluated whether CCE can suppress balloon angioplasty-induced neointima formation and elucidated its possible pharmacological mechanisms. A rat model of carotid arterial balloon angioplasty was established to evaluate the inhibitory effect of CCEs on neointimal hyperplasia. Two cell lines, A10 vascular smooth muscle cells (VSMCs) and RAW264.7 macrophages, were used to investigate the potential regulatory activities and pharmacological mechanisms of CCEs in cell proliferation and migration and in inflammation. Our in vitro results indicated that CCE3, the ethanolic extract of , exerted the strongest growth inhibitory and antimigratory effects on VSMCs. CCE3 blocked the activation of focal adhesion kinase, platelet-derived growth factor receptor- (PDGFRB), and its downstream molecules (AKT and mTOR) and reduced the expression of matrix metalloproteinase-2. In addition, our findings revealed that CCE3 significantly increased the expression of miRNA-132, an inhibitory regulator of inflammation and restenosis, and suppressed the expression of inflammation-related molecules (inducible nitric oxide synthase, cyclooxygenase-2, interleukin- (IL-) 1, and IL-6). Our in vivo study results indicated that balloon injury-induced neointimal hyperplasia was inhibited by CCE3. CCE3 could reduce neointima formation in balloon-injured arteries, and this effect may be partially attributed to the CCE3-induced suppression of PDGFRB-mediated downstream pathways and inflammation-related molecules.
球囊血管成形术诱导的新生内膜增生仍然是一个必须解决的临床问题。提取物（CCE）的生物活性已显示出在预防再狭窄进展方面的潜力。本研究评估了CCE是否能抑制球囊血管成形术诱导的新生内膜形成，并阐明其可能的药理机制。建立了颈动脉球囊血管成形术大鼠模型，以评估CCE对新生内膜增生的抑制作用。使用两种细胞系，A10血管平滑肌细胞（VSMC）和RAW264.7巨噬细胞，来研究CCE在细胞增殖、迁移和炎症方面的潜在调节活性和药理机制。我们的体外研究结果表明，CCE3（[具体植物名称]的乙醇提取物）对VSMC具有最强的生长抑制和抗迁移作用。CCE3阻断了粘着斑激酶、血小板衍生生长因子受体-β（PDGFRB）及其下游分子（AKT和mTOR）的激活，并降低了基质金属蛋白酶-2的表达。此外，我们的研究结果显示，CCE3显著增加了miRNA-132的表达，miRNA-132是炎症和再狭窄的抑制性调节因子，并抑制了炎症相关分子（诱导型一氧化氮合酶、环氧化酶-2、白细胞介素-（IL-）1和IL-6）的表达。我们的体内研究结果表明，CCE3抑制了球囊损伤诱导的新生内膜增生。CCE3可减少球囊损伤动脉中的新生内膜形成，这种作用可能部分归因于CCE3诱导的对PDGFRB介导的下游途径和炎症相关分子的抑制。
