Influence of gender on ethanol-induced ventricular myocyte contractile depression in transgenic mice with cardiac overexpression of alcohol dehydrogenase
Influence of gender on ethanol-induced ventricular myocyte contractile depression in transgenic mice with cardiac overexpression of alcohol dehydrogenase
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DOI：
10.1016/s1095-6433(02)00347-1
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发表时间：
2003-03-01
影响因子：
2.3
通讯作者：
Ren, J
中科院分区：
文献类型：
--
作者：
Duan, JH;Esberg, LB;Ren, J
急性乙醇暴露抑制心室收缩力，并导致长期饮用乙醇的男性和女性的酒精性心肌病。然而，肌病的严重程度存在性别差异，女性对乙醇诱导的组织损伤更敏感。乙醛（ACA）是乙醇的主要氧化产物，其直接的心脏效应和与雌激素的相互作用可能是导致酒精性心肌病发病机制和性别差异的重要原因。本研究旨在比较心脏过度表达乙醇脱氢酶（ADH）（将乙醇转化为ACA）对心室肌细胞对乙醇的心脏收缩反应的影响，这些心室肌细胞分离自年龄匹配的成年雄性和雌性转基因（ADH）和野生型（FVB）小鼠。用IonOptix SoftEdge系统测量机械性能。ACA生产通过气相色谱法进行评估。来自两种性别的ADH肌细胞表现出相似的机械性质，但与FVB肌细胞相比，产生ACA的功效更高。乙醇（80-640 mg/dl）暴露60 min，FVB组和ADH组细胞缩短率均呈浓度依赖性降低。乙醇对细胞缩短的抑制作用在雌性ADH组显著增强，而雄性ADH组无此作用。ADH转基因并没有加剧乙醇诱导的最大缩短/再延长速度的抑制，在任何性别。此外，无论是乙醇或ADH转基因影响缩短和relengthening在雄性或雌性小鼠的持续时间。这些数据表明，女性可能比男性更敏感的ACA引起的心脏收缩抑制，这可能归因于酒精性心肌病的性别差异。(C)2002年爱思唯尔科技有限公司All rights reserved.
Acute ethanol exposure depresses ventricular contractility and contributes to alcoholic cardiomyopathy in both men and women chronically consuming ethanol. However, a gender-related difference in the severity of myopathy exists with female being more sensitive to ethanol-induced tissue damage. Acetaldehyde (ACA), the major oxidized product of ethanol, has been implicated to play a role in the pathogenesis and gender-related difference of alcoholic cardiomyopathy, possibly due to its direct cardiac effect and interaction with estrogen. This study was designed to compare the effects of cardiac overexpression of alcohol dehydrogenase (ADH), which converts ethanol into ACA, on the cardiac contractile response to ethanol in ventricular myocytes isolated from age-matched adult male and female transgenic (ADH) and wild-type (FVB) mice. Mechanical properties were measured with an IonOptix SoftEdge system. ACA production was assessed by gas chromatography. The ADH myocytes from both genders exhibited similar mechanical properties but a higher efficacy to produce ACA compared to FVB myocytes. Exposure to ethanol (80-640 mg/dl) for 60 min elicited concentration-dependent decrease of cell shortening in both FVB and ADH groups. The ethanol-induced depression on cell shortening was significantly augmented in female but not male ADH group. ADH transgene did not exacerbate the ethanol-induced inhibition of maximal velocity of shortening/relengthening in either gender. In addition, neither ethanol nor ADH transgene affect the duration of shortening and relengthening in male or female mice. These data suggest that females may be more sensitive to ACA-induced cardiac contractile depression than male, which may attribute to the gender-related difference of alcoholic cardiomyopathy. (C) 2002 Elsevier Science Inc. All rights reserved.