Hesperidin blocks varenicline-aggravated atherosclerotic plaque formation in apolipoprotein E knockout mice by downregulating net uptake of oxidized low-density lipoprotein in macrophages

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...

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Bibliographic Details
Published in:	Journal of pharmacological sciences Vol. 143; no. 2; pp. 106 - 111
Main Authors:	Koga, Mitsuhisa, Kanaoka, Yuki, Inada, Koshun, Omine, Sai, Kataoka, Yasufumi, Yamauchi, Atsushi
Format:	Journal Article
Language:	English
Published:	Japan Elsevier B.V 01-06-2020 Elsevier
Subjects:	Atherosclerosis Hesperidin Macrophage Oxidized low-density lipoprotein accumulation Varenicline Oxidized low-density lipoprotein accumulation Varenicline Hesperidin Atherosclerosis Macrophage
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1347-8613 1347-8648
DOI:	10.1016/j.jphs.2020.01.012