Although atherosclerosis is the leading cause of death in the so-called affluent societies, there is presently no drug in our pharmacologic armamentarium against disease to either prevent or reverse this insidious killer and debilitant of human lives. Because of this void the First Brook Lodge Symposium on Anti Atherosclerosis Drug Discovery was convened at Brook Lodge in Augusta, Michigan, August 13-15, 1975. The symposium was sponsored by The Upjohn Company and was international in scope, with investi gators attending from such countries as England, Japan, Belgium, and Italy. The symposium focused on the problems associated with the discovery and evaluation of new drugs effective in preventing or reversing atherosclerosis. The thrust of material is centered around animal models useful as tools in the search and evaluation of new drugs. Broadly categorized, the models are nonhuman primates, rabbits, rodents, quail, and tissue culture. The material is a mix of studies on serum lipids and, more importantly, of studies on the artery, irrespective of serum lipid levels. The prevention of arterial lesions, not reduction of serum lipids, is emphasized. A review of all anti-atherosclerotic agents, with the exception of hypolipidemic agents, is included in this volume of the proceedings of the symposium.
Table of ContentsSection 1 Primate Models.- A Model for Therapeutic Interventions on Established Coronary Atherosclerosis in a Nonhuman Primate.- The Nonhuman Primates as Models for Studying Human Atherosclerosis: Studies on the Chimpanzee, the Baboon and the Rhesus Macacus.- Phylogenetic Variability of Serum Lipids and Lipoproteins in Nonhuman Primates Fed Diets with Different Contents of Dietary Cholesterol.- The Baboon in Atherosclerosis Research: Comparison with Other Species and Use in Testing Drugs Affecting Lipid Metabolism.- The Fine Structure of Nonatherosclerotic Intimal Thickening, of Developing, and of Regressing Atherosclerotic Lesions at the Bifurcation of the Left Coronary Artery.- Apo-Lipoprotein Localization in Human Atherosclerotic Arteries.- Section 2 Rabbit Models.- Rabbits as a Model for the Study of Hyperlipoproteinemia and Atherosclerosis.- Seasonal Variations in Severity of Experimental Atherosclerosis in Rabbits.- Study of Drugs Affecting Cholesterol-Induced Atherosclerosis in Rabbits.- Turnover and Aortic Uptake of Very Low Density Lipoproteins (VLDL) from Hypercholesteremic Rabbits as a Model for Testing Antiatherosclerotic Compounds.- Evaluation of Permeability Parameters (Influx, Efflux and Volume of Distribution) of Arterial Wall for LDL and Other Proteins.- Oxygen Diffusion and Atherosclerosis.- Section 3 Rodent Models.- High Volume Screening Procedures for Hypobetalipoproteinemic Activity in Rats.- Biological Activity of a Hypobetalipoproteinemic Agent.- Nonisotopic Method for Estimating Cholesterogenesis in the Rat.- Cholesterol Metabolism in Rats Sensitive to High Cholesterol Diet.- Importance of Sex and Estrogens in Amelioration of Lethal Circulatory Stress Reactions: Relationship to Microcirculatory and Reticuloendothelial System Function.- Inbred Mice and Their Hybrids as an Animal Model for Atherosclerosis Research.- Diet Induced Hypercholesterolemia in the Diabetic and Non-Diabetic Chinese Hamster.- Section 4 Avian Models.- Animal Model for Experimental Atherosclerosis Produced by Selective Breeding of Japanese Quail.- Morphologic Observations on Experimental Atherosclerosis in SEA Japanese Quail.- A Mechanism for Lipid Accumulation and Central Necrosis in Fibrous Plaques.- The Influence of Some Dietary Factors and/or Treadmill Exercise on Rat and Chicken Tissue Lipids and Serum Lipoproteins.- Section 5 Tissue Culture.- Effects of Cholesterol Derivatives on Sterol Biosynthesis.- Mechanism of Inhibition of Cholesterol Uptake by the Arterial Wall.- Lipoprotein Uptake and Degradation by Cultured Human Arterial Smooth Muscle Cells.- The Removal of Cellular Lipids from Landschütz Ascites Cells and Smooth Muscle Cells in Culture.