Alcohol Research Unit, Hospital Clinic, Institut d'Investigació August Pi i Sunyer, Department of Medicine, University of Barcelona, Barcelona, Spain.
Alcohol Clin Exp Res. 2011 Jul;35(7):1220-9. doi: 10.1111/j.1530-0277.2011.01456.x. Epub 2011 Apr 4.
Apoptosis mediates in alcohol-induced heart damage leading to cardiomyopathy (CMP). Myocyte proliferation may compensate for myocyte loss. Myostatin is upregulated after cardiac damage and by alcohol consumption thereby decreasing myocyte renewal. We assess the potential role of alcohol in inducing myocyte apoptosis as well as in inhibiting myocyte proliferation.
Heart samples were obtained from organ donors, including 22 high alcohol consumers, 22 with hypertension, 8 with other causes of CMP, and 10 healthy donors. Evaluation included medical record with data on daily, recent and lifetime ethanol consumption, chest X-ray, left ventricular (LV) function assessed by two-dimensional echocardiography, and LV histology and immunohistochemistry. Apoptosis was evaluated by TUNEL, BAX, and BCL-2 assays. Myocyte proliferation was evaluated with Ki-67 assay. Myostatin activity was measured with a specific immunohistochemical assay. CMP was assessed by functional and histological criteria.
Alcoholic and hypertensive donors with CMP showed higher apoptotic indices than did their partners without CMP. Myostatin activity was higher in alcoholics than in controls, mainly in those with CMP. The increase in myostatin expression in alcoholic CMP was higher than in other groups. The Ki-67 proliferation index increased in all groups with CMP compared to those without CMP, with alcoholics showing a lower increase in this proliferation response.
Alcohol produces cardiac myocyte loss through apoptosis but also partially inhibits myocyte proliferation through myostatin up-regulation. The final result may suppose an imbalance in myocyte homeostasis, with a net loss in total ventricular myocyte mass and progressive ventricular dysfunction.
细胞凋亡介导酒精引起的心脏损伤导致心肌病（CMP）。肌细胞增殖可能代偿肌细胞丢失。心肌抑制素在心脏损伤后和酒精消耗时上调，从而减少肌细胞更新。我们评估酒精在诱导肌细胞凋亡以及抑制肌细胞增殖中的潜在作用。
从器官捐献者中获得心脏样本，包括 22 名高酒精消费者、22 名高血压患者、8 名其他 CMP 原因患者和 10 名健康供体。评估包括病历，其中包括每日、近期和终生乙醇摄入量、胸部 X 光片、二维超声心动图评估的左心室（LV）功能以及 LV 组织学和免疫组织化学。通过 TUNEL、BAX 和 BCL-2 测定评估细胞凋亡。用 Ki-67 测定评估肌细胞增殖。用特定的免疫组织化学测定评估肌肉抑制素活性。通过功能和组织学标准评估 CMP。
酒精和高血压 CMP 供体的凋亡指数高于无 CMP 的供体。酒精组的肌肉抑制素活性高于对照组，主要在 CMP 组中。酒精性 CMP 中肌肉抑制素表达的增加高于其他组。与无 CMP 组相比，所有 CMP 组的 Ki-67 增殖指数均增加，而酒精组的这种增殖反应增加较低。
酒精通过凋亡导致心脏肌细胞丢失，但也通过肌肉抑制素上调部分抑制肌细胞增殖。最终结果可能意味着心肌细胞内稳态失衡，总心室肌细胞质量净损失和进行性心室功能障碍。
