The article presents new evidence indicating that elevated levels of circulating long-chain ceramides can independently predict the risk of atherosclerotic cardiovascular disease (ASCVD), challenging current hypercholesterolemia-centered treatment approaches. The study explores the hypothesis that ceramides activate G protein-coupled receptors (GPCRs), exacerbating atherosclerosis through inflammasome activation. A systematic screening revealed that receptors CYSLTR2 and P2RY6 are crucial mediators in this process. Importantly, genetic and pharmacological inhibition of these receptors successfully mitigated the deleterious effects of ceramides, highlighting potential therapeutic targets for ASCVD management.
Recent findings indicate that circulating long-chain ceramides serve as independent predictors of atherosclerotic cardiovascular disease (ASCVD), thereby suggesting new avenues for therapeutic intervention.
Our systematic study linking ceramide levels to G protein-coupled receptors demonstrated that CYSLTR2 and P2RY6 play critical roles in ceramide-induced inflammasome activation linked to atherosclerosis.
Inhibition of CYSLTR2 and P2RY6, through genetic or pharmacological means, was shown to reduce the negative impact of elevated ceramide levels on atherosclerosis progression.
Despite the established link between ceramides and cardiovascular diseases, the mechanisms by which they influence ASCVD through G protein-coupled receptors remain poorly understood.
#cardiovascular-diseases #long-chain-ceramides #atherosclerosis #g-protein-coupled-receptors #inflammasome-activation
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