REVERSE CHOLESTEROL TRANSPORT

几组人类患者的风险增加

Several groups of human patients at increased risk of atherosclerosis show consistent abnormalities in the sequence of reactions ("reverse cholesterol transport") which carries cholesterol from peripheral cells to the liver. The purpose of these pilot studies is to determine whether the baboon, a model for human macrovascular disease, has in plasma a cholesterol transport pathway similar to that identified in humans; and whether genetic or environmental factors which modify the incidence of atherosclerosis and cholesterol transport in humans, have similar effects in the baboon. The rate of reverse cholesterol transport and its component steps (cholesterol transport into plasma; cholesterol esterification in plasma by lecithin: cholesterol acyltransferase; cholesteryl ester transfer) will be measured in baboon plasma. Initial studies will be of reaction rates in the fasting plasma of normal animals. Subsequent measurements will be in the plasma of abimals with familial inheritance of high or low LDL/HDL ratios or with both HDL and LDL levels decreased in plasma. Postprandial lipemia, which stimulates reverse cholesterol transport in normolipemic humans, will be examined for its effect on reverse cholesterol transport and lipoprotein composition in normal and dyslipoproteinemic baboons. The data obtained will indicate the extent to which the mechanisms which generate and distribute cholesteryl esters in human plasma are reproduced in the baboon. If such a similarity is shown by these pilot experiments, it will make possible an investigation of whether cholesterol deposition in the large vessels is directly related to abnormalities of cholesterol metabolism in the plasma of the same animals.