EARLY INTERVENTION OF AGE RELATED ARTERIAL CHANGES

这项调查的长期目标是确定 饮食干预很早就开始了，是生活会影响a)发展 自发性动脉粥样硬化病变和b)对胆固醇喂养的反应 成人生活中的动脉粥样硬化。据推测，早期刺激 胆固醇分解代谢会增加肝脏胆固醇-7α 在成人生活中持续存在并影响动脉粥样硬化形成的羟基酶活性 回应。具体目标是：1.确定强化的效果 早期生命中的胆固醇分解代谢(通过摄食氯氰胺) 鸽子(和随后恢复储备饮食)：a)随后 自发性动脉粥样硬化的发展及对胆固醇摄入的反应 动脉硬化。2.确定血清的“低反应者”模式 新生儿氯乙咪胺治疗后出现的胆固醇变化 由于a)胆固醇吸收和/或胆汁酸排泄的变化。3. 为了确定新生儿胆碱治疗的效果将持续多长时间 坚持胆汁酸排泄增加，肝脏增多 胆固醇-7α羟基酶活性及其机制。4.确定 A)新生儿胆碱胺治疗会带来哪些变化 动脉胆固醇酯浓度和代谢(测量ACAT， 中性和酸性胆固醇酯水解酶和HMG-CoA还原酶) 这是胆固醇酯显著下降的原因。 胆固醇摄入过程中的蓄积(与对照组相比)。它是 预计这些研究将解释与 新生儿氯苯乙胺治疗的疗效及疗效测定 成年后的动脉粥样硬化反应是否会受到 早期生活中的操控。

The long term objective of this investigation is to determine whether dietary intervention started early is life can influence a) the development of spontaneous atherosclerotic lesions and b) response to cholesterol-fed atherosclerosis in adult life. It is hypothesized that early stimulation of cholesterol catabolism will increase hepatic cholesterol-7alpha hydroxylase activity that persists in adult life and influences atherogenic response. The specific aims are: 1. To determine the effect of enhancing cholesterol catabolism (by feeding cholestyramine) during early life of pigeons (and subsequent return to stock diet) on the: a) subsequent development of spontaneous atherosclerosis and response to cholesterol-fed atherosclerosis. 2. To determine if 'hypo-responder' pattern of serum cholesterol changes noted following neonatal cholestyramine treatment is due to changes in a) cholesterol absorption and/or bile acid excretion. 3. To determine how long the effects of neonatal cholestyramine treatment will persist in terms of increased bile acid excretion and increased hepatic cholesterol-7Alpha hydroxylase activity and its mechanism. 4. To determine a) what changes are brought about by neonatal cholestyramine treatment on arterial cholesteryl ester concentration and metabolism (measurement ACAT, and neutral and acidic cholesteryl ester hydrolases and HMG-CoA reductase) that is responsible for the noted decrease in cholesterol ester accumulation (when compared to controls) during cholesterol feeding. It is anticipated that these studies will explain mechanisms related to the beneficial effects of neonatal cholestyramine treatment and determine whether atherogenic response during adult life can be influenced by manipulation in early life.