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羟基红花黄色素A通过介导Akt信号通路对血小板衍生生长因子-BB诱导的血管平滑肌细胞增殖和迁移的抑制作用

Inhibitory effects of hydroxysafflor yellow A on PDGF‑BB‑induced proliferation and migration of vascular smooth muscle cells via mediating Akt signaling.

作者信息

Song Yanmin, Long Lili, Zhang Ning, Liu Yunhai

机构信息

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Mol Med Rep. 2014 Sep;10(3):1555-60. doi: 10.3892/mmr.2014.2336. Epub 2014 Jun 16.

Abstract

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are key pathological factors in the initiation and progression of vascular disorders, including arteriosclerosis and restenosis following percutaneous coronary intervention (PCI). Hydroxysafflor yellow A (HSYA), the main component of the safflower yellow pigments, has widely been used for the treatment of cardiovascular diseases in traditional Chinese medicine. However, to the best of our knowledge, there are no studies investigating the pharmaceutical effect of HSYA on VSMCs or the underlying molecular mechanism. The present study aimed to investigate the effect of HSYA on platelet‑derived growth factor (PDGF)‑BB‑stimulated VSMC proliferation and migration. HSYA significantly inhibited PDGF‑BB‑stimulated VSMC proliferation and, in response to PDGF‑BB‑stimulation, VSMCs dedifferentiated into a proliferative phenotype. However, HSYA effectively reversed this phenotype switching. In addition, the production of nitrous oxide and cyclic guanosine monophosphate induced by PDGF‑BB was also suppressed by HSYA, and HSYA markedly inhibited PDGF‑BB‑stimulated VSMC migration. Investigation of the molecular mechanism revealed that HSYA inhibited PDGF‑BB‑induced activation of Akt signaling. In addition, HSYA also suppressed PDGF‑BB‑stimulated upregulation of cell cycle related proteins and heme oxygenase‑1. In conclusion, HSYA was able to inhibit PDGF‑BB‑stimulated VSMC proliferation and migration, partially via suppressing PDGF‑BB‑induced Akt signaling activation. Therefore, HSYA may be useful for the prevention and treatment of cardiovascular diseases, including atherosclerosis and restenosis following PCI.

摘要

血管平滑肌细胞(VSMC)的异常增殖和迁移是血管疾病发生和发展的关键病理因素,包括动脉粥样硬化和经皮冠状动脉介入治疗(PCI)后的再狭窄。羟基红花黄色素A(HSYA)是红花黄色素的主要成分,在传统中医中已广泛用于治疗心血管疾病。然而,据我们所知,尚无研究调查HSYA对VSMC的药理作用或潜在的分子机制。本研究旨在探讨HSYA对血小板衍生生长因子(PDGF)-BB刺激的VSMC增殖和迁移的影响。HSYA显著抑制PDGF-BB刺激的VSMC增殖,并且在PDGF-BB刺激下,VSMC去分化为增殖表型。然而,HSYA有效地逆转了这种表型转换。此外,HSYA还抑制了PDGF-BB诱导的一氧化氮和环磷酸鸟苷的产生,并且HSYA显著抑制了PDGF-BB刺激的VSMC迁移。对分子机制的研究表明,HSYA抑制了PDGF-BB诱导的Akt信号通路激活。此外,HSYA还抑制了PDGF-BB刺激的细胞周期相关蛋白和血红素加氧酶-1的上调。总之,HSYA能够抑制PDGF-BB刺激的VSMC增殖和迁移,部分是通过抑制PDGF-BB诱导的Akt信号通路激活实现的。因此,HSYA可能对预防和治疗心血管疾病有用,包括动脉粥样硬化和PCI后的再狭窄。

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