The relationship of serum lipoproteins to atherosclerosis in the cholesterol-fed alloxanized rabbit.

The alloxanized rabbit fed cholesterol develops extreme hyperlipemia and hypercholesteremla and yet develops a lesser degree of atherosclerosis than does the normal animal fed cholesterol. The concentrations of the Sf 12-30 and Sf 20-30 classes of lipoproteins correlate well with athero-sclerosis as finally observed in the alloxanized rabbit, whereas both free and total serum cholesterol correlate negatively with atherosclerosis. In the alloxan-diabetic rabbit, the serum cholesterol is principally carried in the Sf 80-100 and greater classes of lipoproteins, and a metabolic block in the conversion of these lipoproteins to those of Sf 40 and less can be demonstrated. U 'SING THE analytic ultracentrifuge, Gofman and co-workers" 2 have identified several classes of giant, cholesterol bearing lipoproteins in the serum of humans, rabbits, and other animals. One class of these molecules, designated as the Sf 10-20 class,* has been correlated with atherosclerosis in humans,3 and a corresponding Sf 10-30 class has been observed to be associated with athero-sclerosis in the rabbit. A normal rabbit has a negligible concentration of all of these classes of lipoproteins in its serum, with the exception of the Sf 3-12 class. A small quantity of lipoproteins of this class has been found in every normal rabbit studied. As a normal rabbit is fed cholesterol, the lipoproteins of the Sf 3-12 class increase progressively in concentration until a critical * One Sf unit represents a flotation rate of 1 X 10 3 cm. per second per dyne per Gm in a sodium chloride solution of density 1.063 Gm per cc. at 26 C. The lipo-proteins were previously isolated from other serum proteins (and high density lipoproteins) by a prepara-tive ultracentrifuge. Spinco Model L and Model E ultracentrifuges were used. 401 value is reached (which varies from rabbit to rabbit). At this time lipoproteins of successively higher Sf class begin to appear; for instance, the Sf 12-20 class appears in the serum, and after a critical concentration of this class is achieved, the Sf 20-30 class begins to appear." 3 Finally, the entire spectrum of lipoproteins is present in large quantity from chylomicrons (approximately Sf 40,000) to the original Sf 3-12 class. Naturally, these divisions of the spectrum of lipoproteins are necessarily arbitrary. In the original reports by Gofman and associates the Sf 10-30 and Sf 3-10 classes were evaluated as to their relationship with athero-sclerosis in the rabbit. Since that time a few normal rabbits have been …