Nicotine Induces Proinflammatory Responses in Macrophages and the Aorta Leading to Acceleration of Atherosclerosis in Low-Density Lipoprotein Receptor−/−Mice

Abstract

Objective— We investigated the molecular mechanism of nicotine-accelerated atherosclerosis in a hyperlipidemic low-density lipoprotein receptor^−/− mouse model. Methods and Results— Low-density lipoprotein receptor^−/− mice received time-release nicotine or placebo pellets for 90 days. Aortic lesion size was 2.5 times larger in nicotine-treated than in placebo-treated mice (PConclusions— Chronic nicotine exposure augments atherosclerosis by enhancing the production of proinflammatory cytokines by macrophages, which, in turn, activate atherogenic NF-κB target genes in the aortic lesions. We investigated the molecular mechanism of nicotine-accelerated atherosclerosis in the hyperlipidemic LDLR^−/− mouse model. Our findings reveal a novel mechanism of nicotine-mediated atherogenesis. Nicotine directly activates macrophages via the nicotinic acetylcholine receptor, activating multiple downstream events, leading to NF-κB–mediated inflammation in the arterial wall and accelerated atherosclerosis.