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

Understanding of the mechanisms underlying atherosclerotic disorders has evolved beyond the view of a progressive collection of lipids and cellular debris in the vascular wall. Current evidence has implicated inflammatory pathways as an important pathogenic mechanism in atherogenesis and plaque destabilization. Although not necessarily the primary event, inflammation and cytokine activation during plaque formation and destabilization may represent a common final pathway to various stimuli. Thus, it seems that not only 'new' risk factors, such as infections with various microorganisms, but also classic risk factors for cardiovascular disease, such as hyperlipidemia, hypertension and diabetes, may promote their atherogenic effects through inflammatory responses. Indeed, recent reports have suggested that traditional cardiovascular medications may attenuate atherogenesis and enhance plaque stability, at least partly through anti-inflammatory mechanisms. However, uncovering the inflammatory pathways in atherosclerosis has raised the possibility that newer treatment modalities should be more directly targeted against inflammatory mediators. Recently, a series of experimental studies have reported reduction of atherosclerosis by immunomodulatory therapy, such as chemokine blockade, interleukin-10 and immunization/vaccination against oxidized low-density lipoprotein and heat-shock protein. It is conceivable that some of these approaches will be tested clinically and, if successful, they could provide novel treatment strategies in coronary artery disease in humans.
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PMID:Inflammation in coronary artery disease: potential role for immunomodulatory therapy. 1629 1

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease closely associated with obesity, type 2 diabetes and hyperlipidemia. For further understanding of NASH, development and characterization of appropriate animal models with metabolic abnormalities is important. Based on the "two hit theory", we tried to develop a new murine model of NASH with metabolic abnormalities. For the first hit to achieve metabolic abnormalities, a high-fat diet (HFD: 60 cal% fat) was fed to C57BL/6 mice for 10 weeks. For the second hit, 30mg/kg tetracycline was injected intraperitoneally once daily for 10 days. The HFD-fed mice treated with tetracycline showed robust increases in triglyceride content and expression levels of proinflammatory cytokine mRNAs in the liver. In addition, plasma ALT levels were significantly elevated by this combinational treatment. Furthermore, histological examination demonstrated that combinational treatment induced multifocal inflammatory cellular infiltration in the livers of all mice, and thus caused mild steatohepatitis. The HFD-tetracycline model could be useful for further understanding NASH.
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PMID:Development of nonalcoholic steatohepatitis model through combination of high-fat diet and tetracycline with morbid obesity in mice. 1642 58

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.
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PMID:Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice. 1659

Obesity is one of the most frequently encountered medical problems of our time. Among the complications of this pathologic entity, renal disease is an important issue and its pathophysiologic mechanisms are a challenge for the physician, since a variety of etiologic factors are implicated in its genesis. For example, hypertension, hyperlipidemia and insulin resistance affect renal function, each one in a different way. Obesity seems to be a state in which kidneys demonstrate morphological and functional alterations, while hormonal and growth factors play a significant role. Among them, leptin, a recently discovered cytokine, has undergone extended investigation and has proven to be a factor that contributes to renal disease, mainly through mechanisms that involve activation of the TGF-beta system resulting in glomerulopathy and related clinical symptoms. Experiments in animals have revealed interesting aspects as far as the role of leptin in kidney function. Understanding the underlying mechanisms of obesity-related glomerulopathy may become a valuable aid in handling an obese patient with renal disease and associated problems.
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PMID:Obesity and renal disease: a possible role of leptin. 1661 10

There are increasing evidences showing that inflammation participates in atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents should be considered. We have induced chronic, aseptic inflammation upon the injection of turpentine and tested the effect of dexamethasone on lipoprotein metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice. Aseptic inflammation caused a significant decrease in hyperlipidemia. Treatment with dexamethasone elicited the opposite effect increasing hyperlipidemia through mechanisms related to the increase in the synthesis of triglyceride-rich lipoproteins. Changes in plasma lipids correlated with those observed in the size of atherosclerotic lesions. Our data suggest the presence of a common mechanism present in both observations and which is probably related to the cytokine secretion. Among the candidates, we chose to test the effect of interleukin-6 because it is involved in both processes, atherosclerosis and inflammation, and its expression is efficiently repressed by corticosteroids. The injection of recombinant interleukin-6 in our mice elicited the same effects observed in our model of inflammation. We conclude that manipulation of inflammation-related mechanisms modulates lipid homeostasis and development of atherosclerotic plaque in rodents.
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PMID:Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E-deficient mice: a possible role for interleukin-6. 1681 11

One response of the brain to stressors is to increase microglial activation with the consequent production of proinflammatory cytokines like interleukin-1beta (IL-1beta), which has been shown to exert an inhibitory effect on long-term potentiation (LTP) in the hippocampus. It has been consistently shown, particularly in vitro, that amyloid-beta (Abeta) peptides increase activation of microglia, while its inhibitory effect on LTP is well documented, and associated with the Abeta-induced increase in IL-1beta. Here we set out to establish whether the Abeta-induced inhibition of LTP in perforant path-granule cell synapses, was coupled with evidence of microglial activation and to assess whether atorvastatin, which is used primarily in the treatment of hyperlipidaemia but which possesses anti-inflammatory properties, might modulate the effect of Abeta on LTP. We report that intracerebroventricular injection of Abeta increased expression of several markers of microglial activation, and in parallel, inhibited LTP in dentate gyrus. The data show that atorvastatin abrogated the Abeta-induced microglial activation and the associated deficit in LTP. On the basis of the evidence presented, we propose that the action of atorvastatin is mediated by its ability to increase production of the anti-inflammatory cytokine, interleukin-4, which we report mimics several of the actions of atorvastatin in the rat hippocampus.
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PMID:The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-beta1-42 in the rat hippocampus in vivo. 1692 Jan 63

Patients with systemic lupus erythematosus develop accelerated atherosclerosis independent of traditional risk factors. The 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely prescribed for hyperlipidemia, but they also exhibit anti-inflammatory actions that appear to be independent of their suppressive actions on plasma cholesterol levels. In this study, we analyzed the effect of the HMG-CoA reductase inhibitor simvastatin on disease manifestations in gld.apoE-/- mice that lack functional Fas ligand and apolipoprotein E and exhibit accelerated atherosclerosis and aggravated lupus-like features. Wild-type, gld, apoE-/-, and gld.apoE-/- mice were maintained on a high cholesterol Western diet and received daily simvastatin (0.125 mg/kg) or saline for 12 wk. Serum cholesterol levels were unaffected by simvastatin treatment, but atherosclerotic lesion area was reduced in both apoE-/- and gld.apoE-/- mice treated with simvastatin. Simvastatin also reduced the lymphadenopathy, renal disease, and proinflammatory cytokine production seen in gld.apoE-/-, but not gld, mice. The immunomodulatory effects in gld.apoE-/- mice were associated with enhanced STAT6 and decreased STAT4 induction in submandibular lymph node cells. Along with reductions in serum TNF-alpha and IFN-gamma levels, there was also an increase in IL-4 and IL-10 transcript levels in lymph nodes. These data indicate that HMG-CoA reductase inhibitors ameliorate atherosclerosis and lupus-like autoimmunity independent of their cholesterol-lowering effects via a shift from a Th1 to a Th2 phenotype in the gld.apoE-/- model. Thus, the anti-inflammatory activities of statins may have utility for the treatment of both autoimmunity and atherosclerosis in patients with systemic lupus erythematosus.
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PMID:Simvastatin treatment ameliorates autoimmune disease associated with accelerated atherosclerosis in a murine lupus model. 1692 Sep 39

Three-hydroxy-3-methylglutaryl CoA reductase inhibitors, also known as statins, are widely used as the drug of choice for the treatment of hyperlipidemia. However, actions beyond that of simply lowering cholesterol levels have been reported. This study aims at evaluating the effect of atorvastatin on antibody interleukin-4 and gamma-interferon production in mice immunized with egg albumin. Antibody levels were determined by an enzyme linked immunosorbent assay and cytokine transcripts by reverse transcriptase-polymerase chain reaction. Results indicated that repeated daily doses of 40 mg/Kg body weight of atorvastatin following immunization suppressed the antibody response in mice to egg albumin. Moreover, a decline in interleukin-4 and gamma-interferon transcripts was observed.
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PMID:Effect of atorvastatin on antibody, interleukin-4 and gamma-interferon production in mice immunized with egg albumin. 1699 94

Inflammatory states are characterized by decreased food intake, hyperglycemia, and insulin resistance. The contribution of cytokines in this phenotype is important and is exerted through activation of SOCS proteins and inhibition of insulin signaling, as well as through direct stimulation of the ob gene. Obesity, a condition that has reached epidemic rates, is characterized by hyperglycemia, hyperlipidemia, insulin resistance and increased food intake, and body weight. In the following article we summarize the current views of the mechanisms underlying insulin resistance in obesity and the other inflammatory states. We also discuss the regulation of appetite in inflammatory states, and we provide evidence on the cytokine-independent induction of anorexia following immune activation in mice. Understanding of the exact mechanisms regulating these processes may provide important insights for the control of this group of diseases that compromise to a great extent the quality of life and are associated with high mortality.
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PMID:Regulation of appetite and insulin signaling in inflammatory states. 1714 47

Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin (LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators of key enzymes that control lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein receptor-deficient mice, which lack the ability to control lipid levels in the blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin beta receptor decoy protein attenuated the dyslipidemia. These results suggest that the immune system directly influences lipid metabolism and that LT modulating agents may represent a novel therapeutic route for the treatment of dyslipidemia.
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PMID:Lymphotoxin beta receptor-dependent control of lipid homeostasis. 1743 Nov 57


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