Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperlipidemia is common in renal allograft recipients. To elucidate the role of cyclosporine in posttransplant hyperlipidemia, we measured lipids, lipoprotein lipids, and apolipoproteins of thirty-five renal allograft recipients and evaluated their relation to trough cyclosporine blood levels. All patients were on a triple immunosuppressive regimen with equal doses of prednisone and azathioprine, and had stable graft function. Cyclosporine blood levels were significantly correlated to total plasma cholesterol (P = 0.028), low-density lipoprotein cholesterol (P = 0.022), apolipoprotein B (P = 0.017), and the cholesterol/high-density lipoprotein cholesterol ratio (P < 0.002), but not to plasma triglycerides. Significant inverse correlations were found between cyclosporine blood levels and high-density lipoprotein cholesterol (P = 0.034), high-density lipoprotein3 cholesterol (P = 0.025), and apolipoprotein A-1 (P = 0.047), but not high-density lipoprotein2 cholesterol. The independent relation of cyclosporine blood levels to each of the measured lipid parameters was investigated by a stepwise regression model including age, body mass index, interval from transplantation, diabetes mellitus, plasma creatinine, and intake of diuretics and beta-blockers. After correction for these 7 variables, cyclosporine blood levels remained significantly associated with high-density lipoprotein cholesterol, high-density lipoprotein3 cholesterol, apolipoprotein A-1, apolipoprotein B, low-density lipoprotein cholesterol, and the cholesterol/high-density lipoprotein cholesterol ratio. These data suggest that cyclosporine causes atherogenic dyslipidemia.
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PMID:Relation of cyclosporine blood levels to adverse effects on lipoproteins. 819 11

The purpose of this study was to determine the effect of serum lipids, lipoprotein fractions, and apolipoprotein (apo) A-1, B and E on mortality from vascular and nonvascular causes in an unselected elderly population. The random sample of 347 community-living individuals aged 65 years or older was obtained in 1982. Serum total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride, and apo A-1, B and E were determined at baseline. After the 11-year follow-up, 199 of the participants had died, and 148 were still alive. Mortality data from vascular and nonvascular causes by the end of 1993 were obtained from official registers. In the univariate analysis, a low total cholesterol level was associated with death due to both vascular and nonvascular causes (P value for trend, .021 and .0027, respectively). After the adjustment for other risk factors, the inverse association between total cholesterol and vascular mortality disappeared, but low total cholesterol was still a significant predictor of death due to nonvascular causes. Adjusted relative risks (RRs) of death due to nonvascular causes for those with elevated total cholesterol (5.1 to 6.5, 6.6 to 8.0, and > 8.0 mmol/L) compared with the reference group (< or = 5.0 mmol/L) were 0.5 (95% confidence interval [CI], 0.2 to 1.2), 0.6 (0.2 to 1.0), and 0.2 (0 to 0.8), respectively. Neither concentrations of HDL-C, LDL-C, triglyceride, nor apo B were associated with vascular or nonvascular mortality. On the other hand, low concentration of apo A-1 predicted vascular death. The RR for the lowest tertile was 1.6 (1.1 to 2.5) compared with the highest tertile. Furthermore, the occurrence of the apo E e4 allele was associated with increased risk of vascular mortality (RR, 1.5; 95% CI, 1.0 to 2.2), but the risk was not related to the levels of lipids, lipoproteins, or other apolipoproteins at baseline. Nonvascular mortality also tended to be predicted by the presence of the e4 allele (RR, 1.5; 95% CI, 0.9 to 2.5). In an unselected elderly population, the allelic variation of apo E, i.e., the presence of the e4 allele, and a low concentration of apo A-1 were more accurate indicators of vascular mortality than total cholesterol or lipoprotein fractions. The risk associated with the apo E polymorphism is unrelated to dyslipidemia.
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PMID:Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. 926 Dec 50

The lipid profile is known to alter in patients with infection, but there has not been a study of the apolipoprotein levels in serum of otherwise healthy children during infection. Lipids, lipoproteins, apolipoproteins A-1 and B and lipoprotein (a) were evaluated prospectively in 31 consecutive children, aged 4-15 years, who were admitted to the hospital with bacterial pharyngitis. The degree of dyslipidemia associated with bacterial pharyngitis was assessed using each child as his/her own control and by comparison with 79 healthy children who had not had an infection during the past 3 months. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B levels were significantly decreased during the symptomatic phase of the disease, whereas the serum triglyceride level was slightly elevated. Serum lipoprotein (a) concentration did not change significantly. In conclusion, it is suggested that serum lipids, lipoproteins and apolipoproteins should not be assessed during infection because of the possible transient changes of these parameters during infection or inflammation.
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PMID:Should children with infection be tested for lipid, lipoprotein and apolipoprotein? 958

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.
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PMID:Rosuvastatin alone or with extended-release niacin: a new therapeutic option for patients with combined hyperlipidemia. 1553 64

Several new drug therapies with beneficial effects on more than one of the cardiometabolic risk factors that contribute to the metabolic syndrome have been developed recently or are under investigation. Emerging risk factors for coronary heart disease (CHD), including low concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 (apoA-1), high levels of high-sensitivity C-reactive protein, and small dense low-density lipoprotein cholesterol particles, have been identified. We provide a detailed description of the mechanisms of action and findings from clinical trials of the new drug therapies and discuss established drug therapies with beneficial effects on emerging risk factors for CHD. The new and emerging drug therapies include an antiobesity agent that reduces atherogenic dyslipidemia and abnormal glucose metabolism; cholesteryl ester transfer protein inhibitors that increase HDL cholesterol and apoA-1 levels; glitazars that increase HDL cholesterol and decrease triglyceride concentrations, as well as improve abnormal glucose metabolism; and the amylin analog pramlintide and the incretin mimetic exenatide, both of which reduce body weight as well as improve abnormal glucose metabolism. The insulin-sensitizing effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs), which may help prevent new-onset diabetes mellitus, and the beneficial effects of the ARB telmisartan on the glucose and lipid profiles also are presented.
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PMID:New and emerging strategies for reducing cardiometabolic risk factors. 1663 83

Macrophages are central to the initiation and progression of atherosclerosis and thus can be very appropriate targets for therapy. Cell adhesion molecules mediating monocytes recruitment to the endothelium are attractive therapy targets and their inhibitors are in clinical trials. Macrophage scavenger receptors like SR-A and CD-36 mediate foam cell formation by facilitating the uptake of modified lipids. Peroxisome proliferator-activated receptors (PPAR), liver X receptor (LXR)-mediated signaling, mitogen-activated protein kinase (MAPK) induced phosphorylation events seem to play an important role in this phenomenon. Proteins affecting macrophage cholesterol metabolism and transport, including ATP-binding cassette (ABC) A1, ABCG1, acyl-CoA:cholesterol acyltransferase (ACAT), apolipoprotein A-1 (ApoA-1), neutral cholesteryl ester hydrolase (NCEH) also regulate foam cell formation and are being developed as therapeutic targets by many pharmaceutical companies. Macrophage proliferation and apoptosis are important events controlling inflammatory response, plaque vulnerability, and destabilization. Free cholesterol (FC) activates the macrophage endoplasmic reticulum (ER) stress pathway and apoptosis. Free radicals and nitric oxide also modulate macrophage foam cell formation and apoptosis. Various antioxidants like AGI-1067 and BO-653 are in clinical trials for atherosclerosis treatment. Macrophage matrix metalloproteinase's (MMP's) play a significant role in weakening and rupture of plaques. Efforts are on to develop isoform specific MMP inhibitor. CD-14, MMP-3, ABCA1, Toll-like receptor-4 (TLR-4), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), arachidonate lipoxygenase-15 (ALOX-15), and Connexin37 polymorphisms and macrophage dysfunction signify their importance in atherosclerosis. Deciphering the role of macrophages in regulating dyslipidemia and inflammation during atherosclerosis is important for developing them as therapeutic targets.
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PMID:Macrophages: an elusive yet emerging therapeutic target of atherosclerosis. 1800 Sep 63

High fructose consumption is associated with the development of fatty liver and dyslipidemia with poorly understood mechanisms. We used a matrix-assisted laser desorption/ionization-based proteomics approach to define the molecular events that link high fructose consumption to fatty liver in hamsters. Hamsters fed high-fructose diet for 8 weeks, as opposed to regular-chow-fed controls, developed hyperinsulinemia and hyperlipidemia. High-fructose-fed hamsters exhibited fat accumulation in liver. Hamsters were killed, and liver tissues were subjected to matrix-assisted laser desorption/ionization-based proteomics. This approach identified a number of proteins whose expression levels were altered by >2-fold in response to high fructose feeding. These proteins fall into 5 different categories including (1) functions in fatty acid metabolism such as fatty acid binding protein and carbamoyl-phosphate synthase; (2) proteins in cholesterol and triglyceride metabolism such as apolipoprotein A-1 and protein disulfide isomerase; (3) molecular chaperones such as GroEL, peroxiredoxin 2, and heat shock protein 70, whose functions are important for protein folding and antioxidation; (4) enzymes in fructose catabolism such as fructose-1,6-bisphosphatase and glycerol kinase; and (5) proteins with housekeeping functions such as albumin. These data provide insight into the molecular basis linking fructose-induced metabolic shift to the development of metabolic syndrome characterized by hepatic steatosis and dyslipidemia.
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PMID:Proteomic analysis of fructose-induced fatty liver in hamsters. 1864 Mar 90

The principal causes of morbidity and mortality in children with chronic renal failure on maintenance hemodialysis are cardiovascular complications. Recently, it has been suggested that oxidative stress, chronic inflammation and malnutrition are risk factors for cardiovascular disease. However, to date, biomarkers of oxidative stress have not been well studied in children. The aim of this study was to investigate the relationship between oxidative stress and cardiovascular risk factors in children on hemodialysis therapy. Twenty-eight hemodialysis patients (13 females, 15 males; mean age 15.1 +/- 2.5 years) and 20 healthy children (13 females, seven males; mean age 14.3 +/- 2.7 years) were included in the study. Levels of antibodies to oxidized low-density lipoprotein (oLABs), high sensitivity C-reactive protein (hs-CRP), albumin, prealbumin, transferrin, and ferritin were measured. Antibodies to oxidized low-density lipoprotein (LDL) in hemodialysis patients were lower than those in the controls (P < 0.05). The patients with lower oLAB titers had higher levels of hs-CRP and ratio of erythropoietin to hematocrit (EPO/Htc), and lower levels of albumin, prealbumin, apolipoprotein A-1 (ApoA(1)), and high-density lipoprotein (P < 0.05). Antibodies to oxidized LDL in hemodialysis patients with dyslipidemia were lower than those of patients with normal lipid profile (P < 0,05). This study showed that children treated by hemodialysis are exposed to oxidative stress and chronic inflammation. We suggest that oLAB levels are decreased in children on hemodialysis as a result of severe oxidative stress and that these antibodies are related to inflammation, anemia, malnutrition and dyslipidemia.
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PMID:Oxidative stress in children on hemodialysis: value of autoantibodies against oxidized low-density lipoprotein. 1895 4

Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.
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PMID:Pueraria mirifica phytoestrogens improve dyslipidemia in postmenopausal women probably by activating estrogen receptor subtypes. 1906 Apr 49

We recently proposed that the biological markers improved by carbohydrate restriction were precisely those that define the metabolic syndrome (MetS), and that the common thread was regulation of insulin as a control element. We specifically tested the idea with a 12-week study comparing two hypocaloric diets (approximately 1,500 kcal): a carbohydrate-restricted diet (CRD) (%carbohydrate:fat:protein = 12:59:28) and a low-fat diet (LFD) (56:24:20) in 40 subjects with atherogenic dyslipidemia. Both interventions led to improvements in several metabolic markers, but subjects following the CRD had consistently reduced glucose (-12%) and insulin (-50%) concentrations, insulin sensitivity (-55%), weight loss (-10%), decreased adiposity (-14%), and more favorable triacylglycerol (TAG) (-51%), HDL-C (13%) and total cholesterol/HDL-C ratio (-14%) responses. In addition to these markers for MetS, the CRD subjects showed more favorable responses to alternative indicators of cardiovascular risk: postprandial lipemia (-47%), the Apo B/Apo A-1 ratio (-16%), and LDL particle distribution. Despite a threefold higher intake of dietary saturated fat during the CRD, saturated fatty acids in TAG and cholesteryl ester were significantly decreased, as was palmitoleic acid (16:1n-7), an endogenous marker of lipogenesis, compared to subjects consuming the LFD. Serum retinol binding protein 4 has been linked to insulin-resistant states, and only the CRD decreased this marker (-20%). The findings provide support for unifying the disparate markers of MetS and for the proposed intimate connection with dietary carbohydrate. The results support the use of dietary carbohydrate restriction as an effective approach to improve features of MetS and cardiovascular risk.
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PMID:Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. 1908 51


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