Alcohol intake reprograms hepatic immune-metabolic circuits to exacerbate murine atherosclerosis and human cardiovascular risk

作者：Constanze Hoebinger, Georg Semmler, Oleksandr Petrenko, Dragana Rajcic, Dorothea Katharina Hoffelner, Tereza Duckova, Taras P. Baranovskyi, Laura Goederle, My Phung Khuu, Christoph Reinhardt, Petra Pjevac, Joana Séneca, Kamil Mieczkowski, Katharina Burger, Ina Bergheim, Sophie Gensluckner, Andreas Völkerer, T Reiberger, Bernhard Scheiner, Elmar Aigner, Bernhard Wernly, Christian Datz, Christoph J. Binder, Tim Hendrikx · 发表于：JHEP Reports · 年份：2026 · DOI：10.1016/j.jhepr.2026.101932 · 被引用次数：1 · 研究领域：Alcohol Consumption and Health Effects、Liver Disease Diagnosis and Treatment、Alcoholism and Thiamine Deficiency

Background and Aims Recent reclassification of steatotic liver disease (SLD) distinguishes metabolic dysfunction-associated steatotic liver disease (MASLD) from MetALD, a newly defined entity combining MASLD with alcohol consumption. Since the mechanisms linking alcohol consumption in the context of SLD to cardiovascular disease (CVD), the leading cause of SLD mortality, remain elusive, we investigated how metabolic dysregulation and alcohol intake synergistically promote atherosclerosis. Methods Low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice were fed a high-fat, high-cholesterol (HFC) diet with regular or ethanol-containing drinking water (10–20% v/v). Germ-free and antibiotic-treated Ldlr -/- mice were used to assess the contribution of ethanol-induced dysbiosis. Associations between alcohol consumption and cardiometabolic risk were assessed in two human cohorts ( N = 5115, N = 2515). Results Ethanol intake in HFC diet-fed Ldlr -/- mice exacerbated hepatic steatosis and systemic dyslipidemia, despite only modest elevations in systemic ethanol levels ( p s≤0.05). Liver transcriptomic profiling revealed ethanol-induced alterations in lipid metabolism and enhanced proinflammatory signatures, accompanied by increased recruitment of Ly6C high monocytes to the liver ( p =0.0121) and elevated levels in circulation ( p =0.0043). Correspondingly, ethanol-consuming HFC diet-fed Ldlr -/- mice developed enlarged aortic root lesions ( p =0.0105). Neither germ-free conditio...