EARLY INTERVENTION OF AGE RELATED ARTERIAL CHANGES

本次调查的长期目标是确定 早期开始的饮食干预是生活可以影响a）发展 和B）对胆固醇喂养的 动脉粥样硬化。 据推测，早期刺激 胆固醇催化剂会增加肝脏胆固醇-7 α 羟化酶活性在成年期持续存在并影响动脉粥样硬化 反应 具体目标是：1.为了确定增强 胆固醇代谢（通过喂养考来烯胺）在生命早期 鸽子（和随后返回到股票饮食）上：a）随后 自发性动脉粥样硬化的发展和对胆固醇喂养的反应 动脉粥样硬化 2.确定血清中是否存在“低应答”模式 新生儿考来烯胺治疗后观察到的胆固醇变化 由于a）胆固醇吸收和/或胆汁酸排泄的变化。 3. 为了确定多久的影响，新生儿消胆胺治疗将 持续存在胆汁酸排泄增加和肝脏 胆固醇-7 α羟化酶活性及其机制。 4.以确定 a）新生儿考来烯胺治疗对 动脉胆固醇酯浓度和代谢（测量ACAT， 以及中性和酸性胆固醇酯水解酶和HMG-CoA还原酶） 这是导致胆固醇酯显著降低的原因 在胆固醇喂养期间的累积（与对照相比时）。 是 预计这些研究将解释与 新生儿考来烯胺治疗的有益效果和确定 成年期的致动脉粥样硬化反应是否会受到 早期的操纵。

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.