UMLS:C0020473 - FACTA Search

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

Lipoprotein and apolipoprotein parameters were studied in the male Zucker diabetic fatty (ZDF) rat at 10 and 20 weeks of age, corresponding to hyperinsulinemic and insulinopenic type 2 diabetes mellitus, respectively. At both ages, ZDF rats had elevated serum triglycerides, free fatty acids, and corticosterone, whereas 20-week ZDF rats had reduced thyroid hormones. At 10 weeks, the hyperlipidemia was confined to elevations in pre-beta triglyceride-rich (d < 1.006 g/mL) lipoproteins. By 20 weeks, all lipoprotein density fractions were increased compared with lean rats, with substantial increases in both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. In ZDF rats, there was a progressive increase in apolipoprotein B (apo B) from 1.9 times control at 10 weeks to three times control at 20 weeks. The increase in apo B was accompanied by a shift of apo B, particularly B100, from very-low-density lipoprotein (VLDL) into denser lipoproteins corresponding to intermediate-density lipoproteins plus LDLs (1.006 < d < 1.063 g/mL). In Zucker and 10-week ZDF rats, in the presence of hyperinsulinemia, the increase in serum apo B was predominantly apo B48 present in VLDL. By 20 weeks, when ZDF rats are insulinopenic, the mass ratio of B48:B100 shifted from 2.7 to 0.7. The shift was associated with a decrease in hepatic-edited apo B mRNA. Apo E increased in lean rats between 10 and 20 weeks of age. Although apo E also increased in ZDF rats, the increase by 20 weeks was less than that of lean rats. The molar ratio of apo E to B in VLDL was decreased in ZDF rats. In lean rats, greater than 50% of apo E was present in HDL, in contrast to ZDF rats, where less than 20% of apo E was present in HDL. VLDL apo E shifted to denser fractions by 20 weeks of age, similar to apo B. The apo C level was more than double compared with the level in lean rats and was redistributed from the HDL fraction to lipoprotein fractions containing apo B. Both apo A-I and apo A-IV levels more than doubled between 10 and 20 weeks in ZDF rats. The ZDF rat model may be useful in comparative studies of lipoproteins during diabetic progression from hyperinsulinemia to insulinopenia.
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PMID:Lipoprotein alterations in 10- and 20-week-old Zucker diabetic fatty rats: hyperinsulinemic versus insulinopenic hyperglycemia. 982 6

Apolipoprotein A-I (apo A-I) has an important role in the transport of cholesterol. This study describes the complete nucleotide and deduced amino acid sequence for apo A-I of LAP quail. A full length apo A-I cDNA clone for hyperlipidemia atherosclerosis prone (LAP) quail was isolated from a lambda gt10 liver cDNA library. The DNA sequence of LAP apo A-I cDNA was similar to that of normal Japanese quail. The deduced amino acid sequence of LAP apo A-I was hence identical to that of normal Japanese quail. LAP apo A-I mRNA is about 1.4 kilobases in length and expressed in a variety of tissues including small intestine, liver, lung, breast muscle, testis, and heart. Although the tissue distribution of apo A-I was similar between strains, LAP quail expressed more apo A-I mRNA than normal Japanese quail in all tissues examined. This tendency was pronounced with the small intestine. Although the concentration of serum apo A-I did not correlate with the tissue expression of mRNA, the observation may suggest that the increased apo A-I expression in LAP strain had some relevance to the susceptibility of this strain to the experimental atherosclerosis.
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PMID:Apolipoprotein A-I of hyperlipidemia atherosclerosis prone (LAP) quail: cDNA sequence and tissue expression. 1005 18

There is growing evidence of the capacity of vitamin A to regulate the expression of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This region in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined hyperlipidemia (FCHL). The hypothesis tested here was whether vitamin A (retinol), by controlling the expression of the AI-CIII-AIV gene cluster, plays a role in modulating the hyperlipidemic phenotype in FCHL. We approached the subject by studying three genetic variants of this region: a C1100-T transition in exon 3 of the apoC-III gene, a G3206-T transversion in exon 4 of the apoC-III gene, and a G-75-A substitution in the promoter region of the apoA-I gene. The association between plasma vitamin A concentrations and differences in the plasma concentrations of apolipoproteins A-I and C-III based on the different genotypes was assessed in 48 FCHL patients and 74 of their normolipidemic relatives. The results indicated that the subjects carrying genetic variants associated with increased concentrations of apoA-I and C-III (C1100-T and G-75-A) also presented increased plasma concentrations of vitamin A. This was only observed among the FCHL patients, which suggested that certain characteristics of these patients contributed to this association. The G3206-T was not associated with changes in either apolipoprotein concentrations or in vitamin A. In summary, we report a relationship between genetically determined elevations of proteins of the AI-CIII-AIV gene cluster and vitamin A in FCHL patients. More studies will be needed to confirm that vitamin A plays a role in FCHL which might also be important for its potential application to therapeutical approaches.
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PMID:Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial combined hyperlipidemia. 1006 30

In a prospective, uncontrolled multicenter study, we have evaluated the effects of probucol on hyperlipidemia, proteinuria, and glomerular filtration rate (GFR) in hyperlipidemic children with persistent nephrotic syndrome. Probucol was started for a total of 12 weeks in 8 children and for 24 weeks in 14 children. Lipoprotein profiles, serum malondialdehyde (MDA) levels, proteinuria, renal function, and electrocardiogram were monitored every 4 weeks. Side effects were recorded by questionnaire. Treatment was completed by 7 of 8 patients for 12 weeks and by 7 of 14 children for 24 weeks. After 12 weeks, the mean serum concentrations of triglycerides (-15%), total cholesterol (-25%), very low-density lipoprotein-cholesterol (-27%), low-density lipoprotein-cholesterol (-23%), and high-density lipoprotein-cholesterol (-24%), as well as apolipoprotein (apo) A-I (-19%), apo B (-21%), and MDA (-32%) were reduced. The positive effects of probucol on the lipoprotein profile persisted over 24 weeks; however, there was no significant effect on either proteinuria or GFR. In conclusion, probucol had beneficial effects on lipoproteins and lipid peroxidation, but improved neither proteinuria nor GFR. The drug was generally tolerated well, but had to be discontinued because of a prolonged QT interval in 4 of 22 patients.
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PMID:Probucol for treatment of hyperlipidemia in persistent childhood nephrotic syndrome. Report of a prospective uncontrolled multicenter study. 1010 Feb 82

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (<7% of total energy from saturated fat), low-cholesterol (<80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% +/- 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% +/- 1.7%, P < .001), apolipoprotein B (8.2% +/- 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% +/- 2.0%, P = .004) and apolipoprotein B to A-I (5.4% +/- 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.
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PMID:Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet. 1038 Nov 59

Hyperlipidemia in pregnancy accompanying selectively-raised concentrations of serum apolipoprotein A-I (apoA-I) and high-density lipoprotein-2-cholesterol (HDL2-C) had been considered to be, at least in part, mediated by sex hormones. On the other hand, it is known that oral estrogen-replacement therapies in postmenopausal women raise serum concentrations of lipoprotein A-I without apoA-II (LpA-I) originated from the liver. This study was performed to clarify the relations among the concentrations of pre-beta-migrating LpA-I (pre-betaLpA-I) and of serum apoA-I and of HDL-C. And we discussed the origin of pre-beta LpA-I in normal full-term maternal blood. Pre-beta LpA-I concentrations in 12 maternal (mean +/- SD = 33.8 +/- 7.6 mg/dl) and umbilical cord blood (mean +/- SD = 3.1 +/- 1.9 mg/dl) pairs and those in 20 healthy non-pregnant adult female controls (mean +/- SD = 13.5 +/- 6.1 mg/dl) were determined using the crossed immunoelectrophoresis. (1) The higher concentration of maternal pre-beta LpA-I than that of control was contributed to the high concentration of maternal serum apoA-I but not to the high concentration of maternal HDL-C, so it would loosen the correlativity between serum apoA-I concentration and HDL-C concentration because pre-beta LpA-I was cholesterol-poor. (2) It did not correlate with the high concentration of chylomicron, which made us speculate that maternal pre-betaLpA-I might be possible to be originated from the liver by the action of endogenous estrogen. And, (3) no correlation between the concentrations of pre-beta LpA-I from maternal blood and those from cord blood respectively will support the idea that their lipoprotein metabolisms would be independent with each other.
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PMID:[Pre-beta-migrating lipoprotein A-I concentration in normal full-term maternal blood]. 1051 24

Lipoprotein(a) (Lp(a)) is recognized as a new coronary risk factor, but few studies have quantitatively assessed the relationship of serum Lp(a) levels with other coronary risk factors in many patients undergoing coronary cineangiography. Seventeen coronary risk factors were quantified (i.e., age, gender, hypertension, impaired glucose tolerance, cerebrovascular accident, hyperuricemia, smoking, family history of ischemic heart disease (IHD), history of hyperlipidemia, Lp(a), total cholesterol, high density lipoprotein (HDL)-cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoproteins(apo)A-I,B, E) to determine their relationship with the numbers of involved coronary vessels using multiple regression test in 1,006 patients who underwent coronary cineangiogram (280 non-IHD patients: 144 men, 136 women; 726 IHD patients: 460 men, 266 women; age 16-84 years, mean 60.5+/-0.3). Multiple regression test indicated R = 0.506 and items that showed high beta weight and significant p level were age, Lp(a), impaired glucose tolerance, total cholesterol, cerebrovascular accidents, HDL-cholesterol, smoking, gender, family history of IHD, and apo-A-I (0.221, p<0.001; 0.174, p<0.001; 0.616, p<0.001; 0.138, p<0.001; 0.122, p<0.001; -0.12, p<0.001; 0.092, p<0.01; 0.091, p<0.01; 0.067, p<0.05; -0.065, p<0.05; respectively). It was concluded that Lp(a) is an independent, potential, and modifiable coronary risk factor, and that reduction of serum Lp(a) is important in the clinical management of patients with IHD.
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PMID:Lipoprotein(a) is a potential coronary risk factor. 1065 Dec 7

The high incidence of arteriosclerotic disease in patients with chronic renal failure seems to be due to certain peculiarities in their lipid metabolism. These are principally a disorder in the transportation of lipoproteins and a concomitant defect in triglyceride metabolism causing an accumulation of triglyceride-rich-lipoproteins which predispose to atherosclerosis. We studied the disturbances in concentration of apolipoproteins, notably Apo C-II and C-III, which modulate the activity of lipoprotein lipase (LPL), in patients with chronic renal failure (CRF) without replacement therapy and in hemodialysis patients with and without hyperlipidemia. LPL hydrolyses triglycerides in the lipoprotein-triglyceride (LPRTG) core. The main lipid parameters were measured in 4 groups of normolipidemic and hyperlipidemic patients with and without CRF in comparison with healthy controls. We found that the lipolytic activity index (A-I/C-III) was decreased, and Apo C-III levels were increased, in patients with CRF and patients on HD, including normolipidemic patients. We conclude that high Apo C-III levels are found in uremic patients before starting dialysis and do not change during dialysis treatment. This increase could be one of the initial causes of impaired triglyceride catabolism and LPRTG accumulation even in normolipidemic patients with CRF and may be one explanation of the high mortality from cardiovascular disease in these patients.
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PMID:[Apolipoprotein C-II and C-III anomalies in normolipemic and hyperlipemic patients with chronic kidney failure]. 1082 22

The apolipoprotein (apo)A-I/C-III/A-IV gene cluster is involved in lipid metabolism and atherosclerosis. Overexpression of apoC-III in mice causes hypertriglyceridemia and induces atherogenesis, whereas overexpression of apoA-I or apoA-IV increases cholesterol in plasma high density lipoprotein (HDL) and protects against atherosclerosis. Each gene has been studied alone in transgenic mice but not in combination as the entire cluster. To determine which phenotype is produced by the expression of the entire gene cluster, transgenic mice were generated with a 33-kb human DNA fragment. The results showed that the transgene contained the necessary elements to direct hepatic and intestinal expression of the 3 genes. In the pooled data, plasma concentrations were 257+/-9, 7.1+/-0.5, and 1.0+/-0.2 mg/dL for human apoA-I, apoC-III, and apoA-IV, respectively (mean+/-SEM). Concentrations of these apolipoproteins were higher in males than in females. Human apoA-I and apoC-III concentrations were positively correlated, suggesting that they are coregulated. Transgenic mice exhibited gross hypertriglyceridemia and accumulation of apoB(48)-containing triglyceride-rich lipoproteins. Plasma triglyceride and cholesterol concentrations were correlated positively with human apoC-III concentration, and HDL cholesterol was correlated with apoA-I concentration. In an apoE-deficient background, despite being markedly hypertriglyceridemic, cluster transgenic animals compared with nontransgenic animals showed a 61% reduction in atherosclerosis. This suggests that apoA-I and/or apoA-IV can protect against atherosclerosis even in the presence of severe hyperlipidemia. These mice provide a new model for studies of the regulation of the 3 human genes in combination.
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PMID:Expression of human apolipoprotein A-I/C-III/A-IV gene cluster in mice induces hyperlipidemia but reduces atherogenesis. 1103 Dec 14

Genes influence quantitative variations in plasma lipoprotein concentrations. For example, intake of dietary saturated fat and cholesterol raises the average serum cholesterol concentration, leading to a higher risk of coronary artery disease in populations. However, not all individuals within the population are susceptible: genetic factors appear to render individuals either "dietary responsive" or "dietary nonresponsive." In this review, we focus on current knowledge about the influence of genetic polymorphisms in certain genes on the lipoprotein response to dietary fat and cholesterol. Our preliminary studies in the Dietary Intervention Study in Children suggest a significant dose-response relation between the decrease in LDL cholesterol from baseline to 36 mo of follow-up in both the intervention group (who consumed a low-fat, low-cholesterol diet) and the usual care group (who consumed a regular diet) and the presence of the APOA1*A allele at the M1 site and the + site at the M2 site of the gene encoding apolipoprotein (apo) A-I. The DNA polymorphisms on the genes encoding apo A-IV, apo B, apo C-III, apo E, lipoprotein lipase, cholesteryl ester transfer protein, lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol O:-acyltransferase), and LDL receptor were found by others to be associated with the plasma lipoprotein response to dietary intervention. Possible mechanisms involved in these effects are discussed and certain discrepancies in the literature about some genetic effects on responsiveness are analyzed. An improved understanding of the influence of specific genes on lipoprotein responsiveness to dietary fat and cholesterol may allow us to identify and counsel certain individuals to avoid high-fat diets so that they may reduce their risk of developing hyperlipidemia and coronary artery disease.
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PMID:Influence of genetic polymorphisms on responsiveness to dietary fat and cholesterol. 1106 69

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