Response of rhesus serum high density lipoproteins to cycles of diet-induced hypercholesterolemia.

Abstract

Two male rhesus monkeys underwent cyclical feeding of a hypercholesterolemlc diet (2% cholesterol, 25% coconut oil) and a low-fat Purina monkey chow diet. During the latter diet, high density lipoprotein (HDL) exhibited two components with peak densities of d = 1.081 g/ml and 1.109 g/ml named HDL L and HDLH, respectively. During the Initial hypercholesterolemic stage, except for apo A-ll which remained unchanged, there was a transient rise In HDL (mainly HDLJ as well as in HDL cholesterol and apo A-l, all reaching maximal values after about 2 weeks from the onset of the diet. The two HDL species changed neither In size nor density as compared to their baseline counterparts, but had a comparatively higher content In cholesteryl ester and lesser amounts of triglycerides and phospholipids as compared to the normocholesterolemic animal. With the development of overt hypercholesterolemia (plasma cholesterol levels above 400 mg/dl), both HDL particles increased in density due to the loss of surface components (phospholipids and unesterlfled cholesterol) and core triglycerides with only minor changes in protein and cholesteryl ester contents. At this stage, the same two animals exhibited significant changes in the size and buoyant density of LDL. When returned to a normal Purina chow diet, the animals' serum cholesterol levels declined rapidly to normal levels; normalization of the HDL distribution also occurred but at a comparatively later time (26 weeks).Our studies Indicate that the two HDL subsets characteristic of the normocholesterolemic rhesus monkey undergo significant changes in buoyant density as a function of the stage of hypercholesterolemia and that changes In concentration and size mainly affect the HDL L subspecies. At levels of plasma cholesterol below 400 mg/dl, this cholesterol Increment Is reflected by a significant increase in the number of the HDL subspecies without the overt participation of the low density lipoprotein classes characteristic of the advanced hyperlipldemlc stage. Since we previously reported that greatly increased levels of cholesteryl esters enriched low density lipoproteins, (J-VLDL (very low density lipoprotein) and pre-B-VLDL during overt diet-Induced hypercholesterolemia, it is apparent that cholesterol is distributed differently among lipoprotein particles containing either apo A-l, apo B, or apo E depending on its concentration In plasma. (Arteriosclerosis 4:154-164, March/April 1984) R hesus monkeys fed high cholesterol diets develop altered concentrations of plasma lipoproteins. Since there may be a causal relationship between the level of serum low density lipoprotein (LDL) and atherosclerosis, most attention has been focused on LDL. However, the concentration and Received July 7,1983; revision accepted November 18, 1983. density distribution of HDL species are also affected by cholesterol-containing diets. Thus, it was observed that high density lipoprotein (HDL) levels were temporarily increased in rhesus and sooty mangabey monkeys on a high cholesterol diet but fell...

Response of plasma tissue factor pathway inhibitor to diet-induced hypercholesterolemia in crab-eating monkeys.

“…The behavior of HDL-associated TFPI in response to a high-cholesterol diet is rather complicated. As reported by Fless et al, 19 hypercholesterolemia in monkeys reduced the MW of HDL particles after the loss of phospholipid, unesterified cholesterol, and triglyceride. In the present study, we found that high-MW HDLassociated TFPI activity decreased, but low-MW HDLassociated TFPI activity increased in response to a high-cholesterol diet.…”

Atherogenic diet-induced modification of the subfraction distribution of high density lipoproteins in monkeys.

“…316 Thus, we believe that the vertical rotor gradient procedure we have developed preparatively separates the equivalent of the HDL^,, HDLj, and HDLj from plasma of African green monkeys. In this context it is interesting to note that Fless et al, 17 have recently identified subfractions of HDL similar to HDL^, and HDL^ in two rhesus monkeys.…”

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia.

“…It is also of interest that a similar lipoprotein profile (namely, greatly elevated LDL and reduced levels of HDL that are much denser than normal) occurs in rhesus monkeys with diet-induced hypercholesterolemia. 33 ' M Since these animals are not LDL receptor-deficient, this raises the possibility that the perturbation of HDL concentration and density may not be the result of defective LDL processing by the LDL receptor, but could be related in some other way to the elevated LDL levels.…”