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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traditional risk factors for atherosclerosis are well known and their control decreases importantly the appearance of the disease. These factors are the genetic charge, dyslipidemia, smoking, systemic arterial hypertension, diabetes, obesity, gender, age, stress, estrogen levels in women, and life style. However, in the last decade, new risk factors have been identified especially for coronary and cerebrovascular atherosclerosis. Among these factors, the inflammatory process has been pointed out in which acute stage reactants participate, such as C-reactive protein, leukocyte count, globular sedimentation, multiple cytokines, alpha tumor necrosis factor, vascular and cellular adhesion molecules, some metalloproteinases, pregnancy-associated plasma protein A, lipoprotein-associated phospholipase A2, angiotensin II, and very probably infection. This article discusses the mechanism by which these markers participate in the atherosclerotic process and their value as predictors of future coronary events, as well as to what extent current therapeutics can contribute to decrease these events and to improve patient care.
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PMID:[Inflammation in atherosclerosis]. 1296 66

Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
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PMID:[Adipocytokins, obesity and development of type 2 diabetes]. 1459 11

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
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PMID:Obesity as a cardiovascular risk factor. 1467 64

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and by bone loss. We evaluated cross-sectionally the association between periodontal disease and C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (t-PA), LDL-C, von Willebrand factor, and soluble tumor necrosis factor receptors 1 and 2. The final sample consisted of 468 men (ages 47-80 yrs), participating in the Health Professional Follow-up Study, who provided blood and were free of CVD, diabetes, and cancer. In multivariate regression models controlling for age, cigarette smoking, alcohol intake, physical activity, and aspirin intake, self-reported periodontal disease was associated with significantly higher levels of CRP (30% higher among periodontal cases compared with non-cases), t-PA (11% higher), and LDL-C (11% higher). Based on our data, periodontal disease showed significant associations with biomarkers of endothelial dysfunction and dyslipidemia, which may potentially mediate the association between periodontal and cardiovascular disease.
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PMID:Periodontal disease and biomarkers related to cardiovascular disease. 1474 54

Pathways leading from obesity to the manifestations of metabolic syndrome involve a number of metabolic risk factors, as well as adipokines, mediators of inflammatory response, thrombogenic and thrombolytic parameters, and vascular endothelial reactivity. Increased adipose tissue mass contributes to augmented secretion of proinflammatory adipokines, particularly tumor necrosis factor-alpha (TNF alpha), along with diminished secretion of the "protective" adiponectin. In our view, TNF alpha and adiponectin are antagonistic in stimulating nuclear transcription factor-kappa B (NF-kappa B) activation. Through this activation, TNF alpha induces oxidative stress, which exacerbates pathological processes leading to oxidized low-density lipoprotein and dyslipidemia, glucose intolerance, insulin resistance, hypertension, endothelial dysfunction, and atherogenesis. NF-kappa B activation further stimulates the formation of additional inflammatory cytokines, along with adhesion molecules which promote endothelial dysfunction. Elevated free fatty acid, glucose, and insulin levels enhance this NF-kappa B activation and further downstream modulate specific clinical manifestations of metabolic syndrome.
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PMID:A novel pathway to the manifestations of metabolic syndrome. 1498 Dec 9

The global burden of coronary heart disease (CHD) has led to the introduction of international guidelines to minimize the morbidity and mortality that result from this condition. These guidelines recognize the contribution of multiple risk factors to the development of CHD and advocate a multifaceted approach to treatment. Obesity, particularly visceral adiposity, contributes to the clustering of many other risk factors, such as hypertension, insulin resistance/type 2 diabetes and dyslipidemia, within individual patients. The molecular mechanisms underlying the metabolic abnormalities induced by visceral adiposity have yet to be fully elucidated; however, adipocytokines such as adiponectin, tumor necrosis factor-alpha and resistin seem to play an important role in this process. Obesity is a major modifiable CHD risk factor, and the benefits of weight loss are numerous, leading to improvements in several co-morbidities. Guidelines advocate lifestyle changes to correct excess bodyweight and improve the CHD risk factor profile. In addition, pharmacologic therapy is recommended for the management of other risk factors, such as hypertension and dyslipidemia, which may not be adequately controlled by lifestyle changes alone. Lowering low-density lipoprotein cholesterol (LDL-C) levels is the primary target for drug therapy for CHD prevention, and statins are first-line lipid-modifying therapy. The introduction of more efficacious statins with favorable effects on the lipid profile will optimize the control of dyslipidemia. Combining these new treatments with lifestyle changes and drug therapies for managing other CHD risk factors, as part of a multifaceted approach to treatment, will have benefits for CHD prevention.
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PMID:Obesity as the core of the metabolic syndrome and the management of coronary heart disease. 1502 38

The metabolic syndrome (visceral obesity, insulin resistance, type 2 diabetes, and dyslipidemia) resembles Cushing's Syndrome, but without elevated circulating glucocorticoid levels. An emerging concept suggests that the aberrantly elevated levels of the intracellular glucocorticoid reamplifying enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1) found in adipose tissue of obese humans and rodents underlies the phenotypic similarities between idiopathic and "Cushingoid" obesity. Transgenic overexpression of 11 beta-HSD-1 in adipose tissue reproduces a metabolic syndrome in mice, whereas 11 beta-HSD-1 deficiency or inhibition has beneficial metabolic effects, at least on liver metabolism. Here we report novel protective effects of 11 beta-HSD-1 deficiency on adipose function, distribution, and gene expression in vivo in 11 beta-HSD-1 nullizygous (11 beta-HSD-1(-/-)) mice. 11 beta-HSD-1(-/-) mice expressed lower resistin and tumor necrosis factor-alpha, but higher peroxisome proliferator-activated receptor-gamma, adiponectin, and uncoupling protein-2 mRNA levels in adipose, indicating insulin sensitization. Isolated 11 beta-HSD-1(-/-) adipocytes exhibited higher basal and insulin-stimulated glucose uptake. 11 beta-HSD-1(-/-) mice also exhibited reduced visceral fat accumulation upon high-fat feeding. High-fat-fed 11 beta-HSD-1(-/-) mice rederived onto the C57BL/6J strain resisted diabetes and weight gain despite consuming more calories. These data provide the first in vivo evidence that adipose 11 beta-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11 beta-HSD-1 deficiency or inhibition.
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PMID:Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. 1504 7

As an Old World nonhuman primate, baboons have been extensively used for research on dyslipidemia and atherogenesis. With increasing knowledge about the endothelium's role in the initiation and progression of atherosclerosis, the value of the baboon model can be increased by developing it for research on the role of dysfunctional endothelium in atherogenesis. Toward that goal, we have established and validated methods of isolating and culturing baboon femoral artery endothelial cells (BFAECs) and compared baboon endothelial cellular characteristics with those of humans. Our results indicated that baboon and human endothelial cells share similar growth and culture behaviors. As was the case for human endothelial cells, BFAECs responded to tumor necrosis factor (TNF)-alpha stimulation with increased expression of adhesion molecules (maximum increase for intracellular adhesion molecule (ICAM): 1.76 +/- 0.26-fold; vascular cell adhesion molecule (VCAM): 1.65 +/- 0.25-fold; E-selectin: 2.86 +/- 0.57-fold). However, BFAECs were hyporesponsive to lipopolysaccharide (LPS) (range, 0.25-20 microg/mL) in adhesion molecule expression, whereas 1 microg/mL LPS induced 2.14- to 3.71-fold increases in human endothelial cells. The differential responses to LPS were not related to TLR-2 and toll-like receptor (TLR)-4 expression on the cell surface. And baboon microvascular endothelial cells had similar features as BFAECs. We observed constitutive expression of interleukin (IL)-6, IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)-1 in both human and baboon endothelial cells, and these cytokines were further induced by TNF-alpha and LPS. We also demonstrated that the responses to TNF-alpha or LPS varied among baboons maintained under the same dietary and environmental conditions, suggesting that response may be controlled by genetic factors.
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PMID:Comparative analysis of vascular endothelial cell activation by TNF-alpha and LPS in humans and baboons. 1521 Oct 29

Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (P=0.012) and tumor necrosis factor-alpha (TNF-alpha) by 33% (P=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-alpha rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89]; P=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1beta (C-511T), IL-6 (G-174C), TNF-alpha (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.
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PMID:Short- and long-term changes in plasma inflammatory markers associated with preeclampsia. 1569 40


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