Park Kyung-Yeon, Oh Euichaul, Kwak Mi-Kyoung, Jun Hyun Sik, Heo Tae-Hwe
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong, Republic of Korea.
PLoS One. 2016 Mar 7;11(3):e0150791. doi: 10.1371/journal.pone.0150791. eCollection 2016.
Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly decreased aortic lesions compared to those of the pravastatin alone treated group. The combined therapy was markedly more effective than that of the single therapies in terms of foam cell formation, smooth muscle cell proliferation, and inflammatory cytokine levels. These results suggest that pravastatin and sarpogrelate combined therapy may provide a new therapeutic strategy for treating atherosclerosis.
普伐他汀是一种可减轻动脉粥样硬化的降脂药物。然而，动脉粥样硬化的多因素发病机制需要其他具有不同抗动脉粥样硬化机制的药物。我们选择了沙格雷酯作为抗血小板药物，并且由于其潜力巨大但关于其对动脉粥样硬化有益作用的信息较少，所以它是与普伐他汀组成复合药物的一种新成分。给低密度脂蛋白受体敲除小鼠喂食高脂、高胆固醇饮食，并分别单独用普伐他汀、单独用沙格雷酯或两种药物联合治疗。虽然单独使用沙格雷酯并未显著减少动脉粥样硬化斑块面积，但与单独使用普伐他汀治疗的组相比，联合使用普伐他汀显著减少了主动脉病变。在泡沫细胞形成、平滑肌细胞增殖和炎性细胞因子水平方面，联合治疗明显比单一治疗更有效。这些结果表明，普伐他汀和沙格雷酯联合治疗可能为治疗动脉粥样硬化提供一种新的治疗策略。
