EARLY INTERVENTION OF AGE RELATED ARTERIAL CHANGES

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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.