[Quercetin attenuates atherosclerosis by promoting ABCA1/G1-mediated cholesterol efflux and suppressing neutrophil extracellular trap formation].

This study aimed to investigate the effect of quercetin on atherosclerosis(AS) in apolipoprotein E knockout(ApoE~(-/-))mice and the mechanism underlying the regulation of cholesterol efflux mediated by adenosine triphosphate-binding cassette transporter A1/G1(ABCA1/G1) pathway and neutrophil extracellular traps(NETs) formation. An AS model was established by feeding Apo E~(-/-)mice with a high-fat diet. The mice were divided into a blank control group, a model group, an atorvastatin calcium group, and lowand high-dose quercetin groups. Serum levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDLC), high-density lipoprotein cholesterol(HDL-C), interleukin(IL)-6, tumor necrosis factor-α(TNF-α), and IL-1β were measured using biochemical methods. Biliary cholesterol excretion rate was determined by acute bile duct cannulation. Hepatic pathology and aortic plaque area were observed by hematoxylin-eosin(HE) and oil red O staining. Collagen and elastic fiber changes in plaques were evaluated by Masson and Verhoeff's Van Gieson(VVG) staining. CD3 and CD68 protein expressions in the aortic root and the colocalization of citrullinated histone H3(Cit-H3) and myeloperoxidase(MPO) were detected by immunohistochemistry and immunofluorescence double staining, respectively. ABCA1 and ABCG1 protein expressions in liver and aortic tissues were detected by Western blot. The results showed that in the model group, serum levels of TC, TG, LDL-C, IL-6, TNF-α, and IL-1β were significantly elevated, hepatic lipid deposition was pronounced, aortic plaque area was enlarged, collagen deposition and elastic fiber rupture were aggravated, inflammatory cell infiltration and NET formation in plaques were enhanced, whereas serum HDL-C level,biliary cholesterol excretion rate, and ABCA1 and ABCG1 protein expressions decreased. Following quercetin intervention, all these abnormal indicators were significantly improved, as evidenced by reduced blood lipid and inflammatory cytokine levels, alleviated hepatic lipid deposition, decreased aortic plaque area, stabilized collagen and elastic fiber architecuture in plaques, suppressed inflammatory cell infiltration and NET formation, accelerated biliary cholesterol excretion, and upregulated ABCA1 and ABCG1 protein expressions. The effects of quercetin were dose-dependent, and the high-dose group showed comparable efficacy to atorvastatin calcium. In conclusion, quercetin may effectively attenuate the progression of AS in Apo E~(-/-)mice by upregulating ABCA1/G1-mediated cholesterol efflux, inhibiting NET formation, and alleviating inflammatory responses.