ETHANOL AND ATHEROSCLEROSIS

这项研究的目的是调整致动脉粥样硬化饮食， 乙醇对家兔动脉粥样硬化的研究。 粥样硬化 心血管疾病仍然是死亡的主要原因， 在西方社会中， 适量摄入乙醇可能 具有有益的效果，而大量的可能是有害的 血管系统 然而，很少有研究已经进行了任何 乙醇对动脉粥样硬化斑块形成的直接影响。 的 研究的缺乏可能至少部分反映了 给兔子喂食乙醇， 相当于严格测试任何关于乙醇的假设， 动脉粥样硬化在没有诸如 营养不良和体重减轻。 我们想验证一下这个假设， 乙醇的摄入直接影响主动脉的大小和组成， 动脉粥样硬化斑块 高胆固醇喂养的新西兰白色（NZW） 兔和渡边遗传性高脂血症（WHHL）兔，两个 将使用常用的实验动脉粥样硬化模型。 我们 提供了初步证据， 饮食已经设计好了。 我们建议通过以下方式使这种饮食具有致动脉粥样硬化性： 添加胆固醇。 在喂食含乙醇和不含乙醇的饮食后， 我们将研究饮食乙醇对大小的影响， 主动脉粥样硬化病变和血浆胆固醇含量 脂蛋白 基于这些结果， 某些基因的表达对斑块的发展至关重要， 脂蛋白的调节可以在随后的实验中进行检查。 WHHL喂养的常规流质饮食，有和没有乙醇将 以同样的方式检查。 必要的技术和试剂是 在我们的实验室里，我们有兔子的经验。 动脉粥样硬化 该项目很重要，因为营养计划， 在没有乙醇的情况下常规产生动脉粥样硬化的兔子 同时也能提供足够的、可量化的 模拟人类乙醇摄入量的乙醇可以开辟新的领域， 对酒精研究感兴趣的人进行调查， 动脉粥样硬化 证明乙醇对病变大小的影响 胆固醇含量将有助于了解流行病学 研究结果，并导致进一步的实验，可能会定义新的预防 和动脉粥样硬化的治疗方法。 拟议工作 有资格获得"更有经验的研究人员进行测试"的资助 新的方法或技术。"

The aim of the research is to adapt atherogenic diets that contain ethanol to studies of rabbit atherosclerosis. Atherosclerotic cardiovascular disease continues to be the leading cause of death and morbidity in Western societies. Ethanol taken in moderate amounts may have beneficial effects, while large amounts may be deleterious to the vascular system. However, very few studies have been performed of any direct effects of ethanol on atherosclerotic plaque formation. The paucity of studies probably reflects, at least in part, the difficulty of feeding rabbits ethanol in accurately quantifiable and sufficient amounts to test rigorously any hypotheses regarding ethanol and atherosclerosis in the absence of confounding effects of such as malnutrition and weight loss. We wish to test the hypothesis that ethanol ingestion directly affects the sizes and compositions of aortic atherosclerotic plaques. The cholesterol-fed New Zealand White (NZW) rabbit and the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, two frequently used models of experimental atherosclerosis will be used. We provide preliminary evidence that a palatable liquid ethanol-containing diet has been devised. We propose to render this diet atherogenic by adding cholesterol. After feeding this diet with and without ethanol, we shall examine the effects of dietary ethanol on the sizes and cholesterol contents of aortic atherosclerotic lesions and plasma lipoproteins. Based on these results the cellular composition and the expression of certain genes critical in plaque development, and the regulation of lipoproteins may be examined in subsequent experiments. WHHL fed the regular liquid diet, with and without ethanol will be examined the same way. The necessary techniques and reagents are available in our laboratory and we have experience with rabbit atherosclerosis. The project is important because a nutritional plan for rabbits that routinely produces atherosclerosis in the absence of ethanol and one that also can deliver sufficient and quantifiable amounts of ethanol to mimic human ethanol intakes could open up new areas of investigation to those interested in studies of alcohol and atherogenesis. Demonstration of ethanol effects on lesion size and cholesterol content would help in the understanding of epidemiologic findings and lead to further experiments that may define new preventive and therapeutic approaches for atherosclerosis. The proposed work qualifies for funding under "more experienced investigators for testing new methods or techniques."