Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is hypothesised that chronic progressive kidney disease may be mediated by abnormalities of lipid metabolism. A series of self-perpetuating secondary events follows an initial glomerular injury. Increased glomerular basement membrane permeability leads to loss of lipoprotein lipase activators, resulting in hyperlipidaemia. Circulating low-density lipoprotein binds with glycosaminoglycans in the glomerular basement membrane and increases its permeability. Filtered lipoprotein accumulates in mesangial cells and stimulates them to proliferate and produce excess basement membrane material. The proximal tubular cells metabolise some of the filtered lipoprotein and the remainder are altered on passage down the nephron. Luminal apoprotein precipitates, initiating or aggravating tubulo-interstitial disease, if the intraluminal pH is close to the isoelectric point of the apoprotein. The hypothesis offers new approaches to the study of chronic progressive kidney disease by proposing a major pathogenetic role for lipid abnormalities.
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PMID:Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. 612 1

Alterations in lipid metabolism have been reported under treatment of various skin disorders with oral retinoids. In 36 patients, mostly psoriatics, under administration of aromatic retinoid (Ro 10-9359) in various dosages serum triglycerides and cholesterol were estimated; in 25 out of 36 patients lipid analysis of the lipoproteins and apoproteins A (HDL) and B (LDL) has been performed. To reveal possible similarities of lipid changes under the two main retinoids we determined the same parameter in 10 patients with conglobate acne treated orally with 13-cis-retinoic acid (isotretinoin/Ro 4-3780 1mg/kg b.w.). Under both drugs serum triglyceride and cholesterol levels were significantly increased. In contrast to the results under the aromatic derivate the HDL- and LDL-cholesterol fractions were changed under isotretinoin. The apoprotein A (HDL) was found significantly increased under aromatic retinoid. Elevated serum lipids mostly occurred in patients having risk factors such as preexisting lipid abnormalities, obesity, diabetes mellitus, heavy smoking, alcohol abuse and hyperlipemia-inducing drugs. Patients to be treated with these drugs should be carefully followed up in order to minimize the risk for atheromatosis.
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PMID:[Changes in serum lipid fractions as a side effect of oral retinoids]. 621 75

Dietary and insulin-deficiency types of hyperlipidemia were compared in adult normal and streptozotocin-induced diabetic male breeder rats. High beef tallow, high corn oil or low fat diets (BT, CO and LF, respectively) were fed ad libitum for 2 months. Glucose and insulin were measured in plasma and total cholesterol, free cholesterol, cholesteryl ester, triglycerides and apoproteins in very low density, low density and high density lipoproteins (VLDL, LDL and HDL, respectively). Diet did not affect plasma glucose or insulin levels. LDL-triglycerides were higher in BT and diabetic than in CO and LF rats. HDL-free cholesterol levels were higher in CO- and LF-than in BT-fed rats. Diabetes resulted in a decrease in HDL-cholesterol. Diabetic animals had higher HDL-apoA-I (apolipoprotein A-I) levels than did CO- and LF- but not BT-fed rats. VLDL-triglycerides were higher in diabetic than in normal rats, with no dietary differences in normal rats. In LDL, apoB levels were lower and apoE levels were higher in LF-fed rats than in animals fed high fat diets. Diabetes resulted in an increase in LDL-apoB but a decrease in LDL-apoE. HDL-apoE levels were higher, although HDL-apoA-I levels were lower in LF than in high fat-fed rats. The results related to lipoprotein composition supported the hypothesis that excess intake of a diet high in saturated fat may contribute to a metabolic pattern that resembles that of a diabetic state.
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PMID:Lipoprotein lipid and protein responses to dietary fat and diabetes in rats. 622 45

Diet is the common denominator in the treatment of hyperlipidemia. Calorie and alcohol restriction are often prescribed for hypertriglyceridemic subjects. When these subjects lose weight their serum triglycerides often decrease, secondary to a diminution in hepatic triglyceride secretion. There is also a reduction in insulin resistance leading to an improvement in carbohydrate tolerance. Because some hypertriglyceridemic subjects over-synthesize triglycerides after alcohol ingestion, alcohol restriction is important in the dietary therapy of these patients. Although controversial, the restriction of cholesterol and saturated fat intake is often prescribed for hypercholesterolemic subjects. Recent evidence show (a) As the daily absolute cholesterol intake increases, the % absorbed is decreased but the amount absorbed per kg body weight is increased. (b) Hypercholesterolemic subjects differ from normal subjects in their response to cholesterol and fat intake. (c) A high cholesterol and high saturated fat diet increases the cholesterol concentration in all lipoprotein fractions. A low cholesterol and high polyunsaturated fat diet has the opposite effect. (d) These diets also affect serum apoprotein levels (apo B and apo A-I). It is becoming evident that hyperlipidemic subjects respond differently from normal subjects to dietary changes. For these subjects, at greater risk of developing atherosclerosis, dietary therapy is important.
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PMID:Dietary therapy of hyperlipoproteinemias: new understandings. 628 14

Endogenous sex hormone activity results in higher levels of VLDL, LDL, and apo B in males than in females, while HDL and particularly HDL2, and apo A1 levels are lower, apo A2 being reduced to a lesser degree. This sex-related difference appears progressively during puberty. There is increasing elevation of LDL cholesterol, apo B, and VLDL TG in women at the menopause, HDL cholesterol levels either diminishing or remaining constant. These differences in lipoprotein and apoprotein concentrations probably play a major role in protecting women against atherosclerosis development during the period of gonadal activity. Similar differences are provoked by exogenous hormone activity: the androgens increase LDL cholesterol and reduce HDL cholesterol, and total cholesterol is therefore only slightly altered. Estrogens provoke elevation of VLDL TG only at supraphysiological doses of the order of 30-50 mcg ethinyl estradiol. In contrast, reductions in LDL cholesterol and increases in HDL cholesterol occur even after low physiological doses of estrogens. This latter increase is dose-related and can be as high as 20%. The action of progestogens is less clearly defined and depends on the molecule administered, the dosage, and its possible androgenic action. When the latter activity is marked, lipoprotein and apoprotein variations are similar to those resulting from testosterone effects. The influence of sex hormones on the course of idiopathic hyperlipidemias varies. They may have a beneficial effect, but this is a fairly rare event and occurs only in very precise situations: improvement of type 3 hyperlipidemia by low dose estrogen therapy; improvement of moderate isolated hypercholesterolemia in menopausal women with low doses of estrogens, and improvement of type 5 mixed hypertriglyceridemia by certain progestogens such as oxandrolone. They usually produce the opposite effect, however, with marked increases of type 1, 4, and 5 hyperlipidemia under estrogens, sometimes leading to attacks of pancreatitis and elevation of preexisting hypercholesterolemias or mixed hyperlipidemias resulting in vascular accidents due to thrombosis. (author's modified)
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PMID:[Sex hormones and metabolism of lipoproteins]. 634 27

.ur current model for cholesterol transport is summarized in Figure 10. In this figure we have put together the various steps in cholesterol transport that were described previously in this review. Under normal conditions, cholesterol metabolism and transport are well regulated. If the transport system is overloaded for a long time, however, hypercholesterolemia caused mainly by increased plasma LDL may develop in several species, including humans. Under such circumstances reverse transport of cholesterol may also fail, giving rise to deposits of cholesterol. Tissue macrophages may be responsible for this lipid accumulation, because receptor-mediated (adsorptive) endocytosis of lipoprotein-associated cholesterol in these cells is not under negative-feedback control. The deposits are mainly found in tissues poorly supplied with blood and lymph: the skin, tendons, the cornea, and arteries. Overload of cholesterol transport may be the result of too much fat and cholesterol in the diet, giving rise to cholesterol-rich lipoproteins from the gut and to increased production of liver (formula; see text) VLDL, which in humans ends up as LDL. In many individuals, however, no hypercholesterolemia is seen, even after eating large amounts of a "western" diet for decades; others may develop increased LDL on a relatively "prudent" diet. Obviously many of the factors and mechanisms in cholesterol transport are influenced by genetic factors. Although studies of several inborn errors of lipid metabolism have given information about some mechanisms, the quantitatively more important differences in genetic patterns, which determine whether or not a western diet will result in hyperlipidemia, are not well known. Perhaps studies of different forms of apoB and apoE and of HDL subgroups and hyper-alpha-lipoproteinemia will explain why certain individuals develop hypercholesterolemia and premature atherosclerosis. All the recent information related to cholesterol metabolism and transport gives rise to new questions. There are many problems of interest for future research: What are the metabolic differences between the apoB produced in the liver and that produced in the gut? To what extent is the protein moiety of LDL modified in the plasma of blood and lymph and in interstitial tissue? Are such modifications important to whether LDL uptake goes through the classic LDL pathway or through the macrophage (i.e., scavenger?) pathway? Are some changes in apoB important for liver recognition of LDL?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transport of cholesterol. 636 11

Plasma lipoprotein concentration, composition, and size were evaluated in two common familial forms of hypertriglyceridemia and compared with those in normal subjects. The very low density lipoproteins (VLDL) were triglyceride-enriched in familial hypertriglyceridemia (triglyceride/apoprotein B ratio: 25.7 +/- 8.9) as compared to normal (9.6 +/- 12.2, P < 0.001) or familial combined hyperlipidemia (9.7 +/- 3.3, P < 0.001). The diameter of VLDL was larger in familial hypertriglyceridemia (3.27 +/- 0.28 pm) than in familial combined hyperlipidemia (2.87 +/- 0.16 pm, P < 0.02). Although in familial hypertriglyceridemia VLDL tended to be larger, and in familial combined hyperlipidemia VLDL tended to be smaller than normal (3.08 +/- 0.48 pm), neither of these differences were significant. While VLDL was normally distributed in the control population, the size was skewed to larger particles in familial hypertriglyceridemia with fewer small particles (P < 0.05) and skewed to smaller particles in familial combined hyperlipidemia with fewer large particles (P < 0.05). VLDL was reciprocally related to low density lipoproteins (LDL) in familial combined hyperlipidemia (r = -0.80 to -0.87) suggesting that the concentrations of these individual lipoprotein groups were somehow interrelated. There was no significant relationship between these two lipoprotein classes in familial hypertriglyceridemia or in normals. In familial combined hyperlipidemia, the apoprotein A-I/A-II ratio was below normal (P < 0.01) suggestive of low HDL(2) levels. This change in apoprotein composition was independent of VLDL or LDL concentration. In familial hypertriglyceridemia, high density lipoprotein (HDL) cholesterol was reduced (33% below mean normal) and HDL triglyceride was increased (by 46%), while the concentration of apoA-I and apoA-II was normal. VLDL triglyceride was inversely related to HDL cholesterol in familial hypertriglyceridemia (r = -0.74, P < 0.005), but not in familial combined hyperlipidemia. The large, triglyceride-enriched VLDL observed in familial hypertriglyceridemia is compatible with the reported increase in VLDL triglyceride synthesis seen in this disorder. The increase in VLDL apoprotein B synthesis previously reported in familial combined hyperlipidemia was associated with VLDL of normal composition. The changes in HDL cholesterol in these two disorders might reflect exchange of triglyceride between VLDL and HDL or could be related to transfer of surface components during the catabolism of VLDL. The reciprocal relationship between various components of VLDL and LDL seen in familial combined hyperlipidemia, but not in familial hypertriglyceridemia or in normal subjects, might provide some insight into the pathological abnormalities in these disorders. The differences between these two common familial forms of hypertriglyceridemia provide further support that they are distinct entities.-Brunzell, J. D., J. J. Albers, A. Chait, S. M. Grundy, E. Groszek, and G. B. McDonald. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.
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PMID:Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia. 640 42

Serum lipids, apoprotein and lecithin-cholesterol acyltransferase activities were studied in 27 renal transplant recipients with stable and normal renal function (serum creatinine 0.16 mM/l or less) sustained for more than 1 year following grafting. Hypertriglyceridemia, which was characteristic of hyperlipidemia in 18 hemodialyzed patients with chronic renal failure, was no longer manifest in transplant recipients. On the other hand, de novo hypercholesterolemia was observed posttransplant with mean serum levels of 5.82 +/- 1.34 versus 5.01 +/- 0.88 mM/l in 575 normal controls. As to the high-density lipoprotein metabolism, the cholesterol content (1.72 +/- 0.56 mM/l) was significantly higher in transplant patients than in hemodialyzed patients (0.82 +/- 0.31 mM/l). In contrast, no variation in apoprotein A-I levels was found between both groups of patients, which produced an elevated high-density lipoprotein cholesterol:apoprotein A-I ratio. Thus, derangement in the serum lipid profile, although qualitatively different, continued to be present following transplantation, and its relevance to the cardiovascular morbidity in these patients remains to be evaluated.
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PMID:De novo development of hypercholesterolemia and elevated high-density lipoprotein cholesterol: apoprotein A-I ratio in patients with chronic renal failure following kidney transplantation. 641 53

High fat, high cholesterol diets do not produce atherosclerotic lesions in some animal species such as the rat; however, when combined with experimentally induced hypothyroidism, such diets do produce lesions. While the diets or hypothyroidism each induce significant alterations in plasma lipoproteins, the combination produces marked hypercholesterolemia. If the atherosclerosis is related to the hyperlipidemia, the combination regimen could be provoking changes in the structure or compositions of lipoproteins which are not noted with either regimen alone. To test this hypothesis, Sprague-Dawley male rats (approximately 250 g) were treated as follows: Diet(a) = chow + 5% lard and 0.3% Na taurocholate; Diet(b) = Diet(a) + 2% cholesterol; Diet(c) = Diet(b) + 0.1% propylthiouracil (PTU). The major findings were as follows. 1) With Diet(b), slow floating very low density lipoprotein (VLDL) (pre-beta) enriched in cholesteryl esters accumulated in plasma and low density lipoprotein (LDL) disappeared from its usual flotation position. 2) With Diet(c), changes in plasma concentration were more marked but were also qualitatively different. More VLDL accumulated, and distribution of VLDL was shifted toward even slower floating cholesteryl ester-rich particles. VLDL had "broad beta" mobility. Also, a beta-migrating intermediate density lipoprotein (IDL) population appeared. 3) Lipoprotein (d less than 1.019 g/ml) and zonal subfractions of d less than 1.019 g/ml lipoproteins (isolated from rats on cholesterol Diet (b] stimulated [3H]oleate incorporation into cholesteryl esters of fibroblasts and macrophages, while the d less than 1.019 g/ml fractions of 5% fat (Diet(a]-fed rats did not. 4) The major finding of this study was that identically prepared d less than 1.019 g/ml fractions of Chol + PTU-treated rats (Diet(c] were approximately 2.5-fold more stimulatory than the lipoproteins of cholesterol-fed rats. The results could not be explained by differences in cholesterol contents of the cholesterol-rich lipoproteins, but significant differences in the apoprotein compositions of the fraction were found which could be important. The most active fractions had higher apoBL/apoBS and apoE/apoC ratios than less active fractions. Thus, the combination regimen of cholesterol and PTU produced changes in lipoprotein structure and composition which enhanced the abilities of the lipoproteins to interact with cells. The results suggest that analysis of lipoprotein-cell interactions in vitro may be predictive of the atherogenic potential of lipoproteins in vivo and that euthyroidism in rat protects against atherogenic hyperlipidemia.
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PMID:Effects of high cholesterol diets on rat plasma lipoproteins and lipoprotein-cell interactions. 643 Oct 45

Two gene specific probes have been used to identify polymorphic DNA loci on chromosome 11 close to the insulin and apoprotein A-1 genes in a genetic analysis of hypertriglyceridaemic patients with and without co-existing diabetes. Of the 45 patients studied with both probes, 15 were diabetic of whom nine possessed class 3/3 insulin polymorphism genotypes, compared with none in the non-diabetic group (p less than 0.001; chi 2 test). In contrast, an uncommon apolipoprotein A-1 polymorphism was found to be equally distributed in the diabetic and the non-diabetic patients. No co-segregation of these two particular genetic polymorphisms was found in either patient group. The differing associations of the two disease-related polymorphism genotypes in patients with hypertriglyceridaemia with or without co-existing diabetes may possibly reflect differing aetiologies of the hyperlipidaemia.
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PMID:Insulin and apolipoprotein A-1/C-III gene polymorphisms relating to hypertriglyceridaemia and diabetes mellitus. 643 27


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