Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA.
Biochem Biophys Res Commun. 2013 May 10;434(3):439-43. doi: 10.1016/j.bbrc.2013.03.092. Epub 2013 Apr 10.
Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.
动脉粥样硬化是心肌梗死和中风的主要病因,是一种慢性动脉疾病,其特征是血管壁中的脂质沉积和炎症。胆固醇在低密度脂蛋白(LDL)中起着关键作用,在动脉粥样硬化的发病机制中起着关键作用。长春西汀是长春胺的生物碱衍生物,长期以来一直被用作治疗认知障碍的脑血流增强剂。最近的研究表明,长春西汀是一种有效的抗炎剂。然而,其在动脉粥样硬化发病机制中的作用仍未得到探索。在本研究中,我们表明长春西汀可显著减少高脂饮食喂养的 ApoE 基因敲除小鼠的动脉粥样硬化病变形成。在培养的鼠巨噬细胞 RAW264.7 细胞中,长春西汀显著减弱氧化型 LDL(ox-LDL)摄取和泡沫细胞形成。此外,长春西汀可极大地阻断培养的巨噬细胞中 ox-LDL 受体 1(LOX-1)的诱导以及动脉粥样硬化病变中 LOX-1 水平。总之,我们的数据揭示了长春西汀在减少动脉粥样硬化发病机制中的新作用,至少部分是通过抑制 LOX-1 信号通路。鉴于长春西汀的出色安全性,本研究表明长春西汀可能是治疗动脉粥样硬化的治疗候选药物。