Dynamic Aspects of Cholesterol Metabolism in Different Areas of the Aorta and Other Tissues in Man and Their Relationship to Atherosclerosis

Abstract

Tracer doses of cholesterol-4-C¹⁴ were administered to each of 8 patients with limited life expectancies. Chemical determinations of free and esterified cholesterol and determinations of their C¹⁴-specific activities were made in serially collected sera, in tissues, and in the different layers of the abdominal aorta, the intimas of which were separated where possible, into normal-appearing intima, thickened intima, and free-lying lipid material. The turnover times of the free and esterified cholesterol fractions of the various tissues and the portions of those fractions derived from the plasma and by synthesis were calculated from these data. The plasma and liver free cholesterol fractions were in equilibrium at the earliest time, 2.5 days. The free cholesterol fractions of other tissues were in equilibrium with the plasma free cholesterol at later dates. The esterified cholesterol fractions of the various tissues, including liver, were in equilibrium with that of the plasma at later dates than were their free fractions. The findings indicate that a large portion of the cholesterol ester of the plasma is not derived from the liver. The greater part of both the free and ester cholesterols of other tissues was derived from the plasma, although a significant portion was derived by synthesis, except for both fractions of skeletal muscle. The adrenal glands were the most active in the synthesis of free cholesterol. The data indicate that a major portion of adrenal cortical hormones is synthesized directly from acetate, without cholesterol as an intermediary product. A major portion of the cholesterol of the intima was derived from plasma through interchange but a considerable amount of cholesterol was synthesized in the intima. The free-lying lipids in the intima appeared to be inert. Data concerning the changes of the lipid contents of the intima with the development of atherosclerosis have been presented. One patient, who died of a second myocardial infarction, differed from the others in having a longer turnover time of the cholesterol of his intima.