Hesperidin blocks varenicline-aggravated atherosclerotic plaque formation in apolipoprotein E knockout mice by downregulating net uptake of oxidized low-density lipoprotein in macrophages
Hesperidin blocks varenicline-aggravated atherosclerotic plaque formation in apolipoprotein E knockout mice by downregulating net uptake of oxidized low-density lipoprotein in macrophages
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DOI：
10.1016/j.jphs.2020.01.012
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发表时间：
2020-06-01
影响因子：
3.5
通讯作者：
Yamauchi, Atsushi
中科院分区：
文献类型：
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作者：
Koga, Mitsuhisa;Koga, Mitsuhisa;Yamauchi, Atsushi
伐尼克兰是一种广泛使用的有效戒烟药物。我们以前曾报道过实验证据表明伐尼克兰增加心血管事件的风险。伐尼克兰促进载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成这种不良反应可能是由于清道夫受体增加和胆固醇外排转运蛋白减少导致巨噬细胞中氧化低密度脂蛋白（oxLDL）的净摄取增加。然而，尚未提出避免或改善伐尼克兰诱导的心血管事件风险的方案。本研究的目的是检查橙皮苷，柑橘类黄酮，对伐尼克林加重载脂蛋白E基因敲除（ApoE KO）小鼠动脉粥样硬化斑块形成的影响。橙皮苷可抑制伐尼克兰对ApoE基因敲除小鼠主动脉、主动脉弓和主动脉根的加重作用。此外，橙皮苷通过阻断RAW 264.7细胞中CD 36和LOX-1清道夫受体的表达增加以及ABCA 1和ABCG 1胆固醇外排转运蛋白的表达减少来保护伐伦克林增强的oxLDL净摄取。我们的研究结果表明，橙皮苷可以避免或改善伐尼克兰治疗引起的心血管事件的风险。(C)2020作者Elsevier B. V.代表日本药理学会制作和主办。
Varenicline is a widely used and effective drug for smoking cessation. We have previously reported experimental evidence suggesting that varenicline increases the risk of cardiovascular events. Varenicline progresses atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. This adverse effect is likely due to enhanced net uptake of oxidized low-density lipoprotein (oxLDL) in macrophages as a result of increased scavenger receptors and decreased cholesterol efflux transporters. However, a regimen has not yet been presented for avoidance or amelioration of the risk for varenicline-induced cardiovascular events. The aim of this study was to examine the effect of hesperidin, a citrus flavonoid, on varenicline-aggravated atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. Hesperidin inhibited the aggravating effect of varenicline in the whole aorta, aortic arch, and aortic root of ApoE KO mice. In addition, hesperidin protected against varenicline-enhanced oxLDL net uptake by blocking the increased expression of CD36 and LOX-1 scavenger receptors and decreased expression of ABCA1 and ABCG1 cholesterol efflux transporters in RAW 264.7 cells. Our findings suggest that hesperidin can avoid or ameliorate the risk for cardiovascular events induced by varenicline treatment. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.