LBSUN85 Acipimox Normalizes The Cardiac Phenotype Induced By Electronic Cigarettes

Abstract

Abstract Electronic nicotine delivery systems or electronic cigarettes (e-cigarettes) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both among smokers and people who have never smoked. Nicotine can induce lipolysis in adipose tissue, leading to increased serum free fatty acids (FFAs). Increased levels of FFAs are one of the key elements in generating a pro-inflammatory response and lead to ectopic lipid accumulation, lipotoxicity, mitochondrial dysfunction, and DNA damage. Our laboratory has shown that e-cigarettes induce cardiac dysfunction associated with oxidative stress and inflammatory phenotype. We investigated the effects of acipimox, an antihyperlipidemic drug that blocks lipolysis, on e-cigarettes-induced cardiac dysfunction and its associated inflammatory signals and oxidative stress. C57BL/6J wild type mice on high fat diet were exposed to saline, e-cigarette with nicotine (2.4%), e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction was decreased in mice exposed to e-cigarette (2.4%) compared with saline and acipimox. Therefore, acipimox normalized the e-cigarette-induced cardiac dysfunction. Transcriptomic evaluation with Gene Set Enrichment Analysis revealed that e-cigarette treated mice had genes enriched in the G2/M DNA damage checkpoint pathways. These transcriptomic changes were normalized by acipimox. Mice exposed to e-cigarettes had increased circulating levels of M-CSF, IL-6, and FFAs, which were decreased by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1, a marker of oxidative stress. Additionally, treatment with e-cigarette (2.4%) increased the apurinic/apyrimidinic sites. This marker of oxidative DNA damage was normalized by acipimox. Understanding the consequences of e-cigarette use on the cardiovascular system is directly relevant to developing policies related to e-cigarette use. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.