The turnover of cholesterol in human atherosclerotic arteries

Abstract

Previous radioisotopic exchange studies in patients with limited life expectancy have indicated that the tracer cholesterol fed orally or administered intravenously could be detected in the aorta and other arteries at autopsy. Since the labeled cholesterol was incorporated into the plasma lipoproteins after its administration these results demonstrated a measure of equilibration of cholesterol between plasma and arterial tissues. In these patients with terminal disease and generally poor nutritional state, steady state conditions did not usually prevail, and cholesterol turnover in the atheromatous lesions could not be reliably estimated. Hence, a study was made of the equilibration of cholesterol between the plasma and arteries in 13 living humans, without the complication of debilitative terminal illnesses, and during a period of time when the subjects were in a metabolic steady state. This study provided information about the rate of influx of plasma cholesterol into atheromatous arteries and whether the influx rate was different in different arteries, in different lesions, and in different layers of the atheromatous plaque. It is not known whether cholesterol, once it is deposited in the arterial intima, is mobilizable thereafter, thus indicating the possibility of regression of the atheromatous lesions. Experiments on the rhesus monkey have proved that regression of severe atherosclerotic lesions can occur but in man, this problem can never be investigated by such direct means. In the present investigation, isotope exchange studies was used to estimate the minimal influx rates of plasma cholesterol into severely atherosclerotic plaques in patients in a metabolic steady state. It was found that the cholesterol contained in clinically significant and severely obstructive atherosclerotic lesions had the capacity to equilibrate with the plasma cholesterol up to 55±9.0% (SE) for the abdominal aorta by 61-96 days, for example. But the specific radioactivity (sp act) of atheroma cholesterol never equaled the sp act of the plasma cholesterol, despite time periods up to 96 days after the intravenous administration of isotopic cholesterol. The equilibration averaged from 30 to 66% for various arteries. The results are discussed.