Rajendran Naresh K, Liu Weimin, Cahill Paul A, Redmond Eileen M
Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Dublin City University, Dublin, Ireland.
Alcohol Clin Exp Res (Hoboken). 2023 Aug;47(8):1467-1477. doi: 10.1111/acer.15138. Epub 2023 Jul 10.
Alcohol (ethanol) consumption has different influences on arterial disease, being protective or harmful depending on the amount and pattern of consumption. The mechanisms mediating these biphasic effects are unknown. Whereas endothelial cells play a critical role in maintaining arterial health, this study compared the effects of moderate and high alcohol concentrations on endothelial cell function.
Human coronary artery endothelial cells (HCAEC) were treated with levels of ethanol associated with either low-risk/moderate drinking (i.e., 25 mM) or high-risk/heavy drinking (i.e., 50 mM) after which endothelial function was assessed. The effect of ethanol's primary metabolite acetaldehyde (10 and 25 μM) was also determined.
Moderate ethanol exposure (25 mM) improved HCAEC barrier integrity as determined by increased transendothelial electrical resistance (TEER), inhibited cell adhesion molecule (CAM) mRNA expression, decreased inflammatory cytokine (interferon-γ and interleukin 6) production, inhibited monocyte chemotactic protein-1 (MCP-1) expression and monocyte adhesion, and increased homeostatic Notch signaling. In contrast, exposure to high-level ethanol (50 mM) decreased TEER, increased CAM expression and inflammatory cytokine production, and stimulated MCP-1 and monocyte adhesion, with no effect on Notch signaling. Reactive oxygen species (ROS) generation and endothelial nitric oxide synthase activity were increased by both alcohol treatments, and to a greater extent in the 50 mM ethanol group. Acetaldehyde-elicited responses were generally the same as those of the high-level ethanol group.
Ethanol has biphasic effects on several endothelial functions such that a moderate level maintains the endothelium in a nonactivated state, whereas high-level ethanol causes endothelial dysfunction, as does acetaldehyde. These data show the importance of dose when considering ethanol's effects on arterial endothelium, and could explain, in part, the J-shaped relationship between alcohol concentration and atherosclerosis reported in some epidemiologic studies.
酒精（乙醇）摄入对动脉疾病有不同影响，根据摄入量和饮酒模式的不同，其作用可能是保护性的，也可能是有害的。介导这些双相效应的机制尚不清楚。鉴于内皮细胞在维持动脉健康方面起着关键作用，本研究比较了中度和高浓度酒精对内皮细胞功能的影响。
用与低风险/适度饮酒（即25 mM）或高风险/重度饮酒（即50 mM）相关的乙醇水平处理人冠状动脉内皮细胞（HCAEC），然后评估内皮功能。还测定了乙醇的主要代谢产物乙醛（10和25 μM）的作用。
中度乙醇暴露（25 mM）可改善HCAEC屏障完整性，表现为跨内皮电阻（TEER）增加；抑制细胞黏附分子（CAM）mRNA表达；减少炎性细胞因子（干扰素-γ和白细胞介素6）产生；抑制单核细胞趋化蛋白-1（MCP-1）表达和单核细胞黏附；并增加稳态Notch信号传导。相比之下，高浓度乙醇（50 mM）暴露会降低TEER，增加CAM表达和炎性细胞因子产生，并刺激MCP-1和单核细胞黏附，对Notch信号传导无影响。两种酒精处理均增加了活性氧（ROS）生成和内皮型一氧化氮合酶活性，且在50 mM乙醇组中增加程度更大。乙醛引发的反应通常与高浓度乙醇组相同。
乙醇对多种内皮功能有双相作用，即适度水平可使内皮维持在非激活状态，而高浓度乙醇会导致内皮功能障碍，乙醛也是如此。这些数据表明，在考虑乙醇对动脉内皮的影响时，剂量很重要，这可能部分解释了一些流行病学研究中报道的酒精浓度与动脉粥样硬化之间的J形关系。
