Deficiency of 5‐HT2B receptors alleviates atherosclerosis by regulating macrophage phenotype through inhibiting interferon signalling

BACKGROUND AND PURPOSE: ) mice. EXPERIMENTAL APPROACH: mice by employing both pharmacological inhibition and genetic deficiency of 5-HT2BR. Inflammasome activation was elucidated using peritoneal macrophages isolated from 5-HT2BR-deficient mice. KEY RESULTS: mice, exhibiting a strong correlation with the presence of macrophages in plaques. Atherosclerosis was attenuated in mice through pharmacological inhibition and genetic deficiency of 5-HT2BR. Additionally, a significant reduction in atherosclerotic plaque size was achieved through bone marrow reconstitution with 5-HT2BR-deficient cells. 5-HT2BR-deficient macrophages showed attenuated interferon (IFN) signalling, NLRP3 inflammasome activation, and interleukin-1β release. Moreover, macrophages primed with 5-HT2BR deficiency displayed an anti-inflammatory phenotype. CONCLUSION AND IMPLICATIONS: These findings support the hypothesis that 5-HT2BR in macrophages plays a causal role in the development of atherosclerosis, revealing a novel perspective for potential therapeutic strategies in atherosclerosis-related diseases. LINKED ARTICLES: This article is part of a themed issue Drugs and Drug Targets in Metabolic and Chronic Inflammatory Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.20/issuetoc.