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)

Moderate protein restriction throughout pregnancy in the rat leads to relative hyperlipidaemia and blunted insulin responsiveness of lipid fuel supply, and impairs foetal growth. The present study examined the basis for these changes. Isocaloric 8% (vs 20%) protein diets were provided throughout pregnancy. Rats were sampled at 19-20 days of gestation. Protein restriction enhanced triacylglycerol (TAG) secretion rates (estimated using Triton WR 1339) 1.6-fold (P < 0.05) in the post-absorptive state. Insulin infusion (4.2 mU/kg per min) decreased plasma TAG concentrations by 33% (P < 0.05) and 48% (P < 0.05) in control (C) and protein-restricted (PR) pregnant groups, an effect associated with suppression of TAG secretion by 42% (P < 0.05) and 51% (P < 0.01) respectively, in the C and PR groups. Since TAG concentrations decline more rapidly, while TAG secretion is enhanced, TAG utilisation during hyperinsulinaemia is enhanced in the PR group. We evaluated whether these changes were associated with dysregulation of lipolysis using adipocytes from two abdominal depots (mesenteric and parametrial). Noradrenaline-stimulated glycerol release was enhanced in parametrial adipocytes (by 40%; P < 0.05) from PR pregnant rats. The anti-lipolytic action of insulin at low concentrations (< or = 15 microU/ml) was impaired by protein restriction (adipocytes from both depots). There was no evidence for altered intra-hepatic regulation of fatty acid (FA) disposal at the level of carnitine palmitoyltransferase. Our results demonstrate increased post-absorptive production of non-carbohydrate energy substrates (TAG and FA) as a consequence of mild protein restriction during pregnancy. These adaptations contribute to a homeostatic strategy to reduce the maternal requirement for gluconeogenesis from available amino acids, optimising the foetal protein supply. Protein restriction also enhances TAG turnover during hyperinsulinaemia. This effect is not a consequence of abnormal regulation of hepatic lipid metabolism by insulin.
Mol Cell Endocrinol 1998 Jul 25
PMID:Moderate protein restriction during pregnancy modifies the regulation of triacylglycerol turnover and leads to dysregulation of insulin's anti-lipolytic action. 978 99

Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).
Biochem Mol Biol Int 1998 Oct
PMID:Chromium levels in patients with internal diseases. 980 4

Fibrinolysis is essential for maintaining the fluency of blood flow. Attenuated fibrinolytic activity has been frequently detected in coronary artery disease, peripheral vascular diseases, diabetes, hyperlipidaemia and obesity. The biologically active product of fibrinolytic system is plasmin. Generation of plasmin is regulated by plasminogen activators (PA) and their inhibitors (PAI). Vascular endothelial and smooth muscle cells synthesize tissue-type and urokinase-type PA (tPA and uPA) and their major physiological inhibitor, PAI-1. The production of fibrinolytic regulators is modulated by a number of biological factors related to thrombosis and atherosclerosis, including coagulation factors, hormones, growth factors, inflammatory mediators and lipoproteins. Several anticoagulants, including heparin, hirudin and hirulog-1, affect the production of fibrinolytic regulators in vascular cells. Studies in knockout mice demonstrated that mice deficient in PA or plasminogen are susceptible to thrombosis during inflammation or injury. Overexpression of uPA or deficiency of PAI-1 promotes neointima and aneurysm formation, which is probably due to active remodelling of extracellular matrix in vascular wall caused by excess plasmin. Long-term effect of treatment with thrombolytic agents or in atheroscleronic cardiovascular diseases remains to be defined. Future studies on determination of the role of PA and PAI in vascular remodelling may help understand the mechanism for neointima formation and orient the prevention of restenosis following vascular procedures.
Int J Mol Med 1998 Feb
PMID:Vascular cell-derived fibrinolytic regulators and atherothrombotic vascular disorders (Review). 985 42

There is increasing epidemiological evidence in humans which associates low birth weight with later cardiovascular and metabolic disorders including hypertension, insulin resistance, hyperlipidaemia and death from ischaemic heart disease. The molecular mechanisms underlying this link are unknown but fetal glucocorticoid exposure may play a role. In adult mammals, glucocorticoid hormones are involved in control of several physiological processes that maintain homeostasis including coordination of responses to stress. During development, glucocorticoids have important regulatory functions to prepare the organism for metabolic adaptations necessary for extrauterine life. Fetal glucocorticoid load is, in part, regulated by placental and fetal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which catalyses a rapid breakdown of maternal and fetal glucocorticoids into inert products. Supraphysiological doses of glucocorticoids retard fetal growth, and human intrauterine growth retardation is associated with elevated cortisol levels. Recent studies have shown that exposing rats to excessive glucocorticoids in utero reduces birth weight and causes permanent hypertension and hyperglycaemia in the adult offspring. These observations show that glucocorticoids could be the link between low birth weight and later disease. Understanding of the molecular details involved in prenatal glucocorticoid action may provide novel insights into the pathogenesis of common cardiovascular and metabolic disorders.
Int J Mol Med 1998 Nov
PMID:Intrauterine events and the programming of adulthood disease: the role of fetal glucocorticoid exposure (Review). 985 61

Familial hypercholesterolemia (FH), a monogenic disease known to be caused by low-density lipoprotein receptor (LDLR) gene mutations, results in the development of premature atherosclerosis and coronary artery disease in affected individuals. The spectrum of LDLR gene mutations in Russia is poorly known. Using polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP) analysis, followed by DNA sequencing, we have screened selected exons of the LDLR gene in 80 unrelated St. Petersburg FH patients for the presence of mutations. Two new LDLR gene mutations, 347delGCC and E397X, were characterized among individuals with familial hypercholesterolemia in St. Petersburg. The carriers of both mutations possessed highly elevated blood serum cholesterol. Cosegregation of E397X mutation and LDLR gene RFLP haplotypes with hyperlipidemia was demonstrated by family study. Both mutations seem to be specific to Slavic patients.
Mol Genet Metab 1998 Dec
PMID:Two novel low-density lipoprotein receptor gene mutations (E397X and 347delGCC) in St. Petersburg familial hypercholesterolemia. 988 19

We found previously that human bone alkaline phosphatase (AP) was glycated by aseptic incubation with glucose, and partially broken down by reactive oxygen species. In this study, we examined whether selective in vivo glycation of AP molecules occurred in bone tissue, using experimental diabetic rats induced by streptozotocin and spontaneously diabetic rats. Additionally, the effects of hyperlipidemia on bone AP activity were examined. Serum AP activity was significantly elevated after incipient onset of diabetes, and the increased activity originated from the intestinal isozyme. High levels of intestinal AP activity were also observed in rats with hyperlipidemia induced by feeding high-fat or high-fructose chow, but the AP activity in bone tissues was maintained at a constant level. AP activity in bone was reduced after the onset of diabetes. The resulting bone AP molecule bound to an aminophenylboronic acid column, which had affinity for glycated proteins, and contained smaller molecular sizes than the native bone AP. These results suggest that elevated levels of serum AP activity originated from the intestinal isozyme accompanied with hyperlipidemia induced by diabetes. In contrast, the reduced serum levels of AP activity in diabetic rats might be dependent on inactivation of bone AP, which was glycated, followed by partial breakdown of bone AP molecules, possibly due to reactive oxygen species.
Comp Biochem Physiol B Biochem Mol Biol 1998 Dec
PMID:Reduced alkaline phosphatase activity in diabetic rat bone: a re-evaluation. 997 13

Male Fischer 344 rats implanted with a methylcholanthrene-induced sarcoma (MCS), along with normal (or control) animals, were fed diets containing either 10% com oil (CO) or 2% CO + 8% fish oil (FO), designated as diets CO and FO, respectively, in a study designed to determine the effect of dietary FO on serum lipids (in the presence or absence of a tumor) and the growth and fatty acid composition of the MCS. For both diets, MCS-bearing rats had significantly (p < 0.05) higher serum levels of triglycerides, cholesterol, phospholipids, and total lipids than controls. For both controls and tumor-bearers, serum levels of all these lipids were, with the exception of cholesterol for the tumorbearers, significantly lower in rats receiving the FO diet than for the corresponding groups receiving the CO diet. Relative to rats fed the CO diet, those fed the FO diet had significantly higher serum levels of some fatty acids (e.g., 20:5n-3) but significantly lower levels of others (e.g., 18:2n-6), regardless of tumor status. For the tumor-bearers, differences in the levels of fatty acids in MCS tissue reflected differences in the fatty acid composition of total serum lipids. Sarcoma growth was unaffected by diet. Thus, feeding dietary FO resulted in changes in the lipid status of both control and tumor-bearing rats. Since sarcoma growth was unaffected by diet, the reduction in the severity of MCS-induced hyperlipidemia by FO appears to be due to an effect of the oil per se.
Biochem Mol Biol Int 1999 Feb
PMID:Effect of dietary fish oil on tumor-induced hyperlipidemia and tumor growth in rats implanted with a methylcholanthrene-induced sarcoma. 1020 75

Hyperlipidemia has been associated with an increase in the incidence of atherosclerosis. The oxidation of low density lipoprotein (LDL) plays an important role in the initiation and progression of atherosclerosis, one of its effects being the inhibition of endothelium dependent relaxation (EDR). The elevated level of lysophosphatidylcholine (LPC) in oxidatively modified LDL has been shown to be a biochemical factor responsible for the impairment of EDR in vascular ring preparations. Several endothelium-derived modulators are thought to control vascular responsiveness. The present work examined whether acetylcholine (ACh)-induced EDR in rat aorta (pre-contracted with phenylephrine, PE) involved both endothelium-derived nitric oxide (EDNO) and endothelium-dependent hyperpolarizing factor (EDHF) and whether LPC inhibited either of these selectively. Indomethacin (10(-5) M), had no significant effect on EDR, indicating that products of cyclooxygenase, including prostacyclin, are not involved. Treatment with either N(W)-nitro-L-arginine methyl ester (L-NAME, 6.8 microM) to inhibit the production of EDNO or with elevated K+ (15 mM), to block the hyperpolarizing effect of EDHF impaired EDR considerably (each of these shifting the inhibitory dose-response relationship to ACh by almost one log unit); in muscles treated with both of these agents EDR was completely inhibited. In each of L-NAME- and K-treated muscles, the addition of LPC (20 microM) further impaired EDR. LPC did not independently raise the tone of resting- or PE-contracted aorta. We conclude that the inhibition of EDR of rat aorta by LPC involves the actions of both EDNO and EDHF.
Mol Cell Biochem 1999 Jul
PMID:Inhibition of endothelium-dependent vascular relaxation by lysophosphatidylcholine: impact of lysophosphatidylcholine on mechanisms involving endothelium-derived nitric oxide and endothelium derived hyperpolarizing factor. 1048 17

Hepatic lipase is an enzyme which hydrolyzes triglycerides from plasma lipoproteins and thus takes part in the metabolism of intermediate density lipoproteins and high-density lipoproteins. The search described here concentrated on mutations of the HL gene in 129 patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in 184 members of 19 families with familial combined hyperlipidemia. Controls were 100 subjects with favorable lipid values (age 46-51 years). Mutation screening and analysis were performed by temperature-gradient gel electrophoresis, allele-specific restriction genotyping, and sequencing. Six different missense mutations and four different silent mutations were found in the HL gene. The alleles Phe-267 and Gln-343 were detected only once in the patient group with hypertriglyceridemia and hyperalphalipoproteinemia and were not detected in the control group. The allele Met-383 was rare in both patients and controls. We found 9.3% of the patients and only 3.0% of controls to be carrying the Val-73-Met missense mutation. The allele Phe-334 was found in 5.43% of patients and in 2.0% of controls. The difference between the frequencies of these alleles was significant between male patients and male controls (Met-73 P=0.044; Phe-334 P=0.047). Also, the summarized odds ratio of 3.28 (95% confidence interval 1.23-8.73) demonstrates that mutation carriers are significantly more prevalent in the patients. Fifteen carriers of the Met-73 allele were found in six families of the familial combined hyperlipidemia group. Furthermore, six carriers of the Phe-334 allele were found in three families of the same group. In comparison to the controls the summarized odds ratio of 2.45 (95% confidence interval 0.89-6.71) barely missed the level of significance. The linkage between genotype and phenotype was incomplete. These results show an association of the missense mutations Val-73-Met and Leu-334-Phe as susceptibility alleles for combined forms of hyperlipidemia.
J Mol Med (Berl) 1999 Oct
PMID:Mutations of the human hepatic lipase gene in patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in patients with familial combined hyperlipidemia. 1060 8

Adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents against a variety of cancers, but its usefulness is seriously curtailed by the risk of developing heart failure. Available laboratory evidence suggests that an increase in oxidative stress, brought about by increased free radical production and decreased myocardial endogenous antioxidants, plays an important role in the pathogenesis of heart failure. Adriamycin-induced apoptosis and hyperlipidemia may also be involved in the process. Probucol, a lipid-lowering drug and an antioxidant, completely prevents the occurrence of heart failure by reducing oxidative stress as well as by the modulation of apoptosis and high lipid concentrations. Thus, combined therapy with adriamycin and probucol has a high potential for optimizing the treatment of cancer patients.
Mol Cell Biochem 2000 Apr
PMID:Adriamycin-induced heart failure: mechanism and modulation. 1088 30


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