Ischemic Heart Disease, Atherosclerosis, and Longevity

IN THE LATE 1940's Duff and McMillan' 2 made the remarkable observation that alloxan-diabetic rabbits developed equal or higher blood cholesterol levels, but markedly less atherosclerosis, than did nondiabetic rabbits fed an equivalent high-cholesterol diet. From the excessive visible lipemia characteristic of the alloxan-diabetic rabbits in this experiment, Duff and McMillan surmised that the physical state of blood cholesterol might be altered in the alloxanized animals and that this alteration might account for their lower degree of atherosclerosis. During those same years, the difficulties attending the study of serum macromolecules in the ultracentrifuge were understood and resolved.3-5 It was shown that in humans and in several other mammalian species a spectrum of lipoproteins, bearing cholesterol, triglycerides, and phospholipids, existed spontaneously or could be induced by a variety of experimental means. In the rabbit it was demonstrated early6' 7that aortic atherogenesis, at least, was strongly related to the serum level of lipoproteins of a rather narrow size-range, the level of lipoproteins larger or smaller in size being unrelated to the rate of development of the atherosclerotic lesion. The Duff observations were explained when it was demonstrated that the alloxanized, cholesterol-fed rabbit transported its massive concentrations of cholesterol in lipoproteins of Sf values greater than 80, with almost no transport in the form of atherosclerosis-associated Sf 12-40 lipoproteins.7