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)

Hepatic lipase (HL) plays a central role in LDL and HDL remodeling. High HL activity is associated with small, dense LDL particles and with reduced HDL2 cholesterol levels. HL activity is determined by an HL gene promoter polymorphism, by gender (lower in premenopausal women), and by visceral obesity with insulin resistance. The activity is affected by dietary fat intake and selected medications. There is evidence for an interaction of the HL promoter polymorphism with visceral obesity, dietary fat intake, and with lipid-lowering medications in determining the level of HL activity. The dyslipidemia with high HL activity is a potentially proatherogenic lipoprotein profile in the metabolic syndrome, in Type 2 diabetes, and in familial combined hyperlipidemia.
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PMID:Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. 1263 74

The aim of this study was to examine how major components of the insulin resistance (IR) syndrome relate to each other and to cardiovascular disease (CVD) in postmenopausal women in 4 ethnic groups. Baseline data from the Women's Health Initiative (WHI) on 3,083 50- to 79-year-old women (1,635 white, 802 black, 390 Hispanic, and 256 Asian/Pacific Islander) were examined. Participants underwent a personal interview and a physical examination, blood samples were drawn, and a detailed cardiovascular history was ascertained. Factor analysis was used to assess the clustering and interdependence of groups of CVD-related IR syndrome variables. Four factors were identified. An obesity factor included IR in all groups and had a significant association with CVD in white (P =.0001) and Hispanic (P =.0024) women. A dyslipidemia factor (high-density lipoprotein [HDL], triglycerides, and HDL2: total HDL ratio) also included insulin and IR and was significantly correlated with CVD in black (P=.0006) and Hispanic (P =.0217) women and had a borderline association in white women (P =.068). Total and low-density lipoprotein (LDL) cholesterol did not relate to CVD in any group. Blood pressure was related weakly to CVD in white women (P =.0434) and strongly in black women (P =.0095). Components of the IR syndrome appear to be associated with CVD in postmenopausal women, although the magnitude of these relationships differed by ethnicity.
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PMID:Risk factor clustering in the insulin resistance syndrome and its relationship to cardiovascular disease in postmenopausal white, black, hispanic, and Asian/Pacific Islander women. 1264 77

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution. A MEDLINE search was conducted for clinical studies reporting the effects of niacin on lipoprotein subclasses. The niacin-associated elevations in HDL cholesterol likely stem from differential drug effects on subclasses, producing favorable changes in levels of HDL2 and apolipoprotein A-I. Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses. In addition, it also tends to decrease concentrations of the larger very-low-density lipoprotein subclasses. Niacin confers diverse benefits with respect to both the quantity and quality of lipid and lipoprotein particles.
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PMID:The effects of niacin on lipoprotein subclass distribution. 1553 65

In human organism, the administration of nicotinic acid (niacin) leads to two types of effects. Within the physiological range (approximately = 20 mg/day), niacin has a vitamin-like role as pellagra preventing factor. The pharmacological dosage (approximately 0,5-4,5 g/day) substantially influences the plasma lipid and lipoprotein concentrations: decreases VLDL and LDL concentrations, changes the profile of LDL subfractions towards the larger particles as well as particles with lower density; it also profoundly increases the concentration of HDL-C in consequence of elevated concentration of HDL2 subfraction. Niacin as the only hypolipidemic drug reduces the lipoprotein(a) concentration. The hypolipidemic mechanism of niacin is different from that of other hypolipidemic drugs. On the basis of clinically controlled trials (both interventional epidemiological and angiographical), which satisfy the criteria of evidence-based medicine, it is possible to conclude that niacin falls unambiguously into the class of hypolipidemic drugs with proven beneficial effect not only on cardiovascular mortality and morbidity, but also on total mortality. Therefore, niacin should have an indisputable role in the pharmacological control of dyslipidemias. With the respect of basic mechanism (inhibition of the lipolysis of adipose tissue) with subsequent decrease in the concentration of free fatty acids and their flux to liver, niacin fulfils the criteria for pathogenetic treatment of atherogenic dyslipidemia in metabolic syndrome. The prerequisite condition for the niacin treatment is the respect for serious adverse effects and possible health hazards of administration (skin flush, hepatotoxicity and deterioration of glucose homeostasis). Recently discovered extrahypolipidemic effects of niacin (antioxidative activity, facilitation of reverse cholesterol transport, activation of PPAR-gamma, antithrombotic effects) and the introduction of drug forms with sustained (extended resp.) release of active compound (that minimizes the adverse effects and administration hazards) form together the basis for firm statement that the derivatives of nicotinic acid should be introduced to the clinical practice in Czech Republic.
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PMID:[Nicotinic acid: an unjustly neglected remedy]. 1716 12

Patients with rheumatoid arthritis (RA) are at risk of cardiovascular disorders. Pathogenesis of rapidly developing atherosclerosis in RA remains to be elucidated. The aim of this study was to compare cholesterol content in serum lipoprotein subfractions in patients with RA and healthy subjects and to establish relationship between lipid profile variations, severity of the disease, and plasma levels of anti-inflammatory cytokines. The study included 15 patients with active RA and 120 healthy subjects of comparable sex and age. RA was found to be associated with a significant decrease of cholesterol of high density (HDL2) and intermediate density (IDL) lipoproteins and its elevation in low density lipoproteins (LDL1-3). There was negative correlation between the latter parameter and disease activity index. No relationship between lipoprotein cholesterol and serum interleukins (IL-6, IL-8) TNF-alpha, and IFN-gamma) was documented. It is concluded that patients with RA exhibit proatherogenic changes of cholesterol content in different lipoprotein subfractions related to the severity of the disease. Further studies are needed to elucidate molecular mechanisms of dyslipidemia in RA and to ensure the choice of optimal targets for therapeutic modalities reducing the risk of cardiovascular disorders.
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PMID:[Relationship between blood lipid spectrum and activity of the disease in patients with rheumatoid arthritis]. 1922 8

Cardiovascular disease is the major cause of death in women in developed countries. Dyslipidemia is highly prevalent in women, particularly after the menopause. Elevated low-density lipoprotein cholesterol (LDL-C) has been identified as the key lipid parameter in both genders whereas HDL-cholesterol and triglycerides have been more closely associated, in some studies, with cardiovascular risk in women. Menopause has been shown to be associated with an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol (predominantly in the HDL2 subfraction). Despite its beneficial effects on the lipid profile, hormone replacement therapy is not recommended for primary or secondary prevention of cardiovascular disease in women. The latest meta-analysis of statin trials with gender-specific outcomes showed a similar benefit in women and men. The addition of ezetimibe to simvastatin in patients with acute coronary syndromes showed a further reduction of the primary endpoint in both genders. While there are no gender-related differences in drug treatment of dyslipidemia, current guidelines, to avoid overtreatment, strongly suggest risk estimation before initiating lipid-lowering treatment in women without manifest cardiovascular disease.
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PMID:Dyslipidemia and cardiovascular disease in women. 2602 98

Atherogenic mixed dyslipidemia associates with oxidative stress and defective HDL antioxidative function in metabolic syndrome (MetS). The impact of statin treatment on the capacity of HDL to inactivate LDL-derived, redox-active phospholipid hydroperoxides (PCOOHs) in MetS is indeterminate. Insulin-resistant, hypertriglyceridemic, hypertensive, obese males were treated with pitavastatin (4 mg/day) for 180 days, resulting in marked reduction in plasma TGs (-41%) and LDL-cholesterol (-38%), with minor effects on HDL-cholesterol and apoAI. Native plasma LDL (baseline vs. 180 days) was oxidized by aqueous free radicals under mild conditions in vitro either alone or in the presence of the corresponding pre- or poststatin HDL2 or HDL3 at authentic plasma mass ratios. Lipidomic analyses revealed that statin treatment i) reduced the content of oxidizable polyunsaturated phosphatidylcholine (PUPC) species containing DHA and linoleic acid in LDL; ii) preferentially increased the content of PUPC species containing arachidonic acid (AA) in small, dense HDL3; iii) induced significant elevation in the content of phosphatidylcholine and phosphatidylethanolamine (PE) plasmalogens containing AA and DHA in HDL3; and iv) induced formation of HDL3 particles with increased capacity to inactivate PCOOH with formation of redox-inactive phospholipid hydroxide. Statin action attenuated LDL oxidability Concomitantly, the capacity of HDL3 to inactivate redox-active PCOOH was enhanced relative to HDL2, consistent with preferential enrichment of PE plasmalogens and PUPC in HDL3.
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PMID:Statin action enriches HDL3 in polyunsaturated phospholipids and plasmalogens and reduces LDL-derived phospholipid hydroperoxides in atherogenic mixed dyslipidemia. 2758 80

Accumulating clinical evidence has suggested serum triglyceride (TG) is a leading predictor of atherosclerotic cardiovascular disease, comparable to low-density lipoprotein (LDL)-cholesterol (C) in populations with type 2 diabetes, which exceeds the predictive power of hemoglobinA1c. Atherogenic dyslipidemia in diabetes consists of elevated serum concentrations of TG-rich lipoproteins (TRLs), a high prevalence of small dense low-density lipoprotein (LDL), and low concentrations of cholesterol-rich high-density lipoprotein (HDL)2-C. A central lipoprotein abnormality is an increase in large TG-rich very-low-density lipoprotein (VLDL)1, and other lipoprotein abnormalities are metabolically linked to increased TRLs. Insulin critically regulates serum VLDL concentrations by suppressing hepatic VLDL production and stimulating VLDL removal by activation of lipoprotein lipase. It is still debated whether hyperinsulinemia compensatory for insulin resistance is causally associated with the overproduction of VLDL. This review introduces experimental and clinical observations revealing that insulin resistance, but not hyperinsulinemia stimulates hepatic VLDL production. LDL and HDL consist of heterogeneous particles with different size and density. Cholesterol-depleted small dense LDL and cholesterol-rich HDL2 subspecies are particularly affected by insulin resistance and can be named "Metabolic LDL and HDL," respectively. We established the direct assays for quantifying small dense LDL-C and small dense HDL(HDL3)-C, respectively. Subtracting HDL3-C from HDL-C gives HDL2-C. I will explain clinical relevance of measurements of LDL and HDL subspecies determined by our assays. Diabetic kidney disease (DKD) substantially worsens plasma lipid profile thereby potentiated atherogenic risk. Finally, I briefly overview pathophysiology of dyslipidemia associated with DKD, which has not been so much taken up by other review articles.
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PMID:Pathophysiology of Diabetic Dyslipidemia. 2999 13

Renal diseases have been recognized as a major cause of secondary dyslipidemia since the late 1950's. Two main pathological conditions of renal diseases, impaired renal function and severe proteinuria (nephrotic syndrome), are individually or conjointly associated with altered lipid metabolism depending on the primary diseases. An impaired renal function causes reductions in lipoprotein and hepatic TG lipase activity, the VLDL recep- tor abundance, and ApoC-II to apoC-III ratio, as well as in ApoA-I and LCAT activities. These alterations result in reduced VLDL clearance and the disturbance of HDL synthesis and maturation, leading to uremic dyslipidemia: increased levels of TG, IDL-C, and small-dense LDL-C and decreased levels of HDL-C. Lipid disorders in nephrotic syndrome (NS) are characterized by increased levels of LDL-C and/or TG. NS-induced hypoalbuminemia enhances the synthesis of cholesterol, cholesterol ester, and ApoB, leading to the increased production of LDL and VLDL. Recently, two intriguing molecules were newly identified as inhibitors of lipoprotein clearance. Pro-protein Convertase Subtilisin/Kexin type 9 (PCSK9) is upregulated in NS, and decreases LDL clearance via prompting degradation of the LDL receptor, while angiopoietin-like 4 (Angptl4) is also induced in NS and restricts VLDL clearance via inhibiting lipoprotein lipase. NS impairs HDL maturation from HDL3 to HDL2 due to a reduction of LCAT, with HDL-C levels preserved. Finally, considering that diabetic nephropathy is representative of progressive renal disease and that gluco- corticoids are an anchor drug for the treatment of NS, diabetes- or drug-associated dyslipidemia is occasional- ly superimposed on the original renal dyslipidemia. [Review].
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PMID:[Renal Dyslipidemia]. 3069 62


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