Quercetin Attenuates Atherosclerotic Inflammation by Inhibiting Gal-3-NLRP3 Signaling Pathway.

Scope Atherosclerosis is the underlying pathogenesis of cardiovascular events caused by inflammation, and dietary intervention has been recommended as one fundamental prevention strategy. Herein, we investigated the anti-arteriosclerotic properties of quercetin by modulating galectin-3 (Gal-3)-NLR family, pyrin domain-containing 3 (NLRP3) pathway. Methods and results Atherosclerotic plaques from ApoE-/- mice fed by high-fat diet (HFD) with or without quercetin intervention (100 mg/kg·bw) for 16 weeks, and carotid plaques from patients with carotid stenosis were collected for histopathological examinations and molecular mechanism assays. Quercetin significantly alleviated atherosclerotic lesions and reduced lipid retention caused by HFD. Proteomic technology identified Gal-3 was increased by HFD but lowered by quercetin. Furthermore, immunofluorescence and immunohistochemistry exhibited higher expressions of Gal-3 and NLRP3 in carotid plaques and plaques from HFD-fed mice, which were concurrently downregulated by quercetin. Similar to TD139, quercetin dramatically suppressed NLRP3 inflammasome activation in ox-LDL-laden macrophages, and accordingly alleviated cellular steatosis and IL-1β secretion, which was abolished by recombinant Gal-3. Co-immunoprecipitation showed Gal-3 binding to NLRP3 promoted inflammasome activation. Conclusion Gal-3 initiates inflammatory lesions by activating NLRP3 inflammasome which functions as a candidate target of quercetin exerting favorable anti-atherogenic effects. Our findings highlight a promising strategy for atherosclerosis prevention and treatment by naturally-occurring quercetin. This article is protected by copyright. All rights reserved.