Biomedical subjects

G M Fless

Publications and source records attributed to G M Fless.

57 records · Page 4Linked to original sources

PubMedDate not supplied

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

Two male rhesus monkeys underwent cyclical feeding of a hypercholesterolemic 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 HDLL and HDLH, respectively. During the initial hypercholesterolemic stage, except for apo A-II which remained unchanged, there was a transient rise in HDL (mainly HDLL) as well as in HDL cholesterol and apo A-I, 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 unesterified 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 HDLL 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 hyperlipidemic stage. Since we previously reported that greatly increased levels of cholesteryl esters enriched low density lipoproteins, beta-VLDL (very low density lipoprotein) and pre-beta-VLDL during overt diet-induced hypercholesterolemia, it is apparent that cholesterol is distributed differently among lipoprotein particles containing either apo A-I, apo B, or apo E depending on its concentration in plasma.

Animals↗

PubMedDate not supplied

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia.

The possibility that low high density lipoprotein (HDL) levels may add to the risk of occlusive atherosclerosis in familial hypercholesterolemia (FH) is supported by the frequency and severity of this finding in these patients, particularly homozygotes. To investigate this abnormality in greater detail, we measured HDL lipid and apoprotein values in nine homozygotes with FH. Compared to their unaffected relatives, they had markedly reduced HDL cholesterol and apo A-I and A-II levels. The values found in heterozygote relatives were between those of homozygotes and those of controls. Density gradient ultracentrifugation of serum or isolated HDL from homozygotes demonstrated little or no HDL2; there was also a shift of homozygotes' HDL to an above normal peak density (d = 1.15 g/ml). Heterozygotes had milder abnormalities. The reduced HDL in FH seems to be related to elevated low density lipoprotein levels although the pathophysiology is unknown. These findings add weight to the concept that HDL abnormalities contribute to the relentless course of atherosclerosis in familial hypercholesterolemia.

Adolescent↗

PubMedDate not supplied

Comparative study of density distribution of plasma lipoproteins of normo- and hypercholesterolemic rhesus monkeys and humans.

Density gradient centrifugation was used to characterize the lipoprotein distribution of rhesus monkeys and human subjects with normal and elevated cholesterol levels. The lipoprotein profile of control monkeys differed from that of normal humans in that their density distribution as a whole was shifted to lower density. The most striking difference was that both rhesus high density lipoprotein (HDL) subspecies had densities lower than human HDL3, with one component having a lower, and the other a higher, density than human HDL2. Rhesus monkeys fed a diet supplemented with 0.5% cholesterol and 15% lard were divided into two groups. Those animals with cholesterol levels less than 435 mg/dl had a high apo A-I concentration and HDL subspecies similar to human HDL2 and HDL3, whereas those with concentrations greater than 435 mg/dl had a low apo A-I concentration and HDL species with a density either similar to, or exceeding that, of human HDL3. Low density lipoprotein (LDL) density decreased in both groups of hypercholesterolemic monkeys and was particularly pronounced in animals with cholesterol levels above 435 mg/dl. When the lipoprotein profiles of normal humans were compared with those having hypercholesterolemia, increases in the density of both HDL2 and HDL3 in hypercholesterolemic men and to a lesser extent in the density of HDL2 in women were detected. The results indicate that the overall density distribution of plasma lipoprotein is different between rhesus monkeys and humans, and may vary within each species as a function of the nutritional status. It follows that it is difficult to define lipoprotein classes of one species by using density intervals determined for another. Furthermore, these intervals can be inadequate in identifying lipoprotein classes within an individual before and after dietary manipulations.

Age Factors↗