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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.
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PMID:Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis. 1834 7

Adipokines are substances produced by the adipose tissue that may play significant roles in the mechanisms contributing to the development of atherosclerosis. Thiazolidinediones have been shown to improve endothelium-dependent vasodilation and to exert multiple antiatherosclerotic effects. This study tested the hypotheses that nondiabetic patients with cardiovascular risk factors have altered levels of adipokines that can be modified by pioglitazone treatment. Eighty patients with hypertension or hypercholesterolemia were in a double-blinded, placebo-controlled, crossover study. In each treatment phase, patients received pioglitazone 45 mg/day or placebo for 8 weeks. Endothelial function studies and biochemical assays were performed at the end of each 8-week treatment period. Twenty-two normal volunteers, matched with patients for age, gender, and body mass index, were recruited as a control group. Compared with controls, placebo-treated patients had lower adiponectin levels (11,160 +/- 763 vs 6,078 +/- 385 ng/ml, p <0.001) and similar plasma leptin levels (21.5 +/- 3.8 vs 16.2 +/- 1.5 ng/ml, p = 0.128) and resistin levels (5.1 +/- 0.4 vs 4.4 +/- 0.2 ng/ml, p = 0.250). In patients, pioglitazone treatment markedly increased adiponectin (+121%, p <0.001) and decreased resistin (-10.5%, p = 0.03). Leptin was not significantly decreased (-7.1%, p = 0.10). In multivariate analysis, pioglitazone-induced changes in endothelial reactivity to acetylcholine were the only significant predictor of increases in adiponectin. In conclusion, in nondiabetic patients with major cardiovascular risk factors, pioglitazone treatment beneficially influences circulating adipokine levels. The relation between the increase in adiponectin levels and the improvement in endothelial vasodilator activity suggests a mechanistic link between vascular effects and adiponectinemia.
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PMID:Effects of peroxisome proliferator-activated receptor-gamma activation with pioglitazone on plasma adipokines in nondiabetic patients with either hypercholesterolemia or hypertension. 1835 18

Leptin and adiponectin are adipokines with respective pro-atherogenic and anti-atherogenic properties, defining the plasma leptin/adiponectin ratio as a novel marker for atherosclerosis. In non-renal patients, both hyperleptinemia and hypoadiponectinemia are associated with cardiovascular complications. In peritoneal dialysis (PD) patients, the leptin/adiponectin ratio is markedly elevated, which is consistent with their increased cardiovascular risk. As glucose metabolism regulates adipokines, we hypothesized that glucose and/or other PD fluid components may affect adipokine production balance. This review summarizes the available data arising from research in this area. In 3T3-L1 adipocytes, glucose-based PD4 1.36% significantly increased leptin secretion vs amino-acid-based (AA) and icodextrin (ICOD)-based PD fluids. In contrast, adiponectin secretion was significantly reduced by PD4 1.36% vs glucose-free dialysates. Glucose concentration in PD fluids was shown to determine leptin secretion. Preliminary data from PD patients showed that a single 6-h dwell with PD4 3.86% glucose acutely increased plasma leptin vs AA (P<0.05). The reduction in glucose load in a standard PD regimen was associated with an improvement in the plasma leptin/adiponectin ratio at 6 months. pH-neutral PD fluids increased leptin secretion in vitro vs acidic PD fluids, without effect on adiponectin. Whether this effect may have an impact on plasma leptin levels in PD patients is unknown. In conclusion, glucose-based PD fluids worsen the adipokine production balance in vitro while glucose-free solutions improve it. In PD patients, hypertonic glucose-based PD fluids may increase plasma leptin levels. Glucose-sparing PD regimens appear to improve the leptin/adiponectin ratio. However, their potential to reduce cardiovascular complications needs to be demonstrated.
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PMID:The leptin/adiponectin ratio: potential implications for peritoneal dialysis. 1837 33

Chronic inflammation, which is widely seen in long-term dialysis patients, is associated with malnutrition, atherosclerosis and an increased mortality risk. The relationship between inflammation and nutrition is certainly bidirectional with inflammation affecting nutritional status and dietary factors influencing the state of inflammation. Cytokines, such as IL-6 and TNF-alpha, interfere with the satiety center inducing loss of appetite, delayed gastric emptying and catabolism of skeletal muscle protein. High adipokine levels may also contribute to the development of malnutrition. On the other hand, dietary factors may interfere directly or indirectly with inflammatory activity. For example, dietary AGEs intake may aggravate inflammation while natural antioxidants, such as polyphenolic flavones or vitamin C from fruits and vegetables may even decrease inflammatory activity. Although there is a lack of good prospective nutritional studies in CKD patients, the individual patient should be advised to follow a more Mediterranean-style diet, restrain from broiling meats in order to avoid dietary AGEs, and take multivitamins regularly.
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PMID:Potential interplay between nutrition and inflammation in dialysis patients. 1845 61

Adiponectin is one of several, important metabolically active cytokines secreted from adipocytes. Low circulating levels of this adipokine have been associated epidemiologically with obesity, insulin resistance, type II diabetes, and cardiovascular disease. To determine if adiponectin can modulate lipid metabolism in macrophages, we expressed the adiponectin gene in human THP-1 macrophage foam cells using a lentiviral vector expression system and demonstrated that macrophages transduced with the adiponectin gene had decreased lipid accumulation compared with control macrophages transduced with the LacZ gene. Macrophages transduced with the adiponectin gene also exhibited decreased oxidized low-density lipoprotein (oxLDL) uptake and increased HDL-mediated cholesterol efflux. Additional studies suggest two potential mechanisms for the reduced lipid accumulation in these adiponectin-transduced macrophage foam cells. The first mechanism involves the PPARgamma and LXR signaling pathways which up-regulate the expression of ABCA1 and promote lipid efflux from these cells. The second mechanism involves decreased lipid uptake and increased lipid hydrolysis which may result from decreased SR-AI and increased SR-BI and HSL gene activities in the transformed macrophage foam cells. We also demonstrated that the expression of two proatherogenic cytokines, MCP-1 and TNFalpha, were decreased in the adiponectin-transduced macrophage foam cells. These results suggest that adiponectin may modulate multiple pathways of lipid metabolism in macrophages. Our studies provide new insights into potential mechanisms of adiponectin-mediated alterations in lipid metabolism and macrophage foam cell formation which may impact the development of atherosclerosis.
Atherosclerosis 2009 Jan
PMID:Adiponectin reduces lipid accumulation in macrophage foam cells. 1851 Oct 57

Obesity often co-presents with other cardiometabolic risk factors such as dyslipidaemia, insulin resistance and hypertension. Less well appreciated is that dysregulation of adipokine production by excess adipose tissue also promotes a state of low-level systemic chronic inflammation and a prothrombotic state, implicated in the development of both atherosclerosis and subsequently cardiovascular events. Lifestyle modification and pharmacological therapy can reduce cardiometabolic risk, a benefit that may be partly due to their effects on adipokine levels.
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PMID:Adipokines--targeting a root cause of cardiometabolic risk. 1855 May 81

Retinol-binding protein-4 (RBP4), a 21-kDa protein synthesized in the liver and adipose tissue, has recently been described as a murine adipokine involved in the development of insulin resistance. The expression of the gene encoding RBP4 was increased in the adipose tissue, but not in the liver, of insulin-resistant adipose GLUT4(-/-) mice and five other mouse models of obesity and insulin resistance. In addition, intraperitoneal injection or transgenic overexpression of RBP4 in mice induced insulin resistance. While experimental clinical approaches (mostly applying clamp techniques) in humans confirmed correlations of RBP4 with insulin resistance, studies in larger groups out of clinical routine failed to demonstrate a connection with alternative measures of insulin sensitivity. Yet, significant associations of RBP4 with atherogenic lipids were found and a focus of future studies should be the influence on atherosclerosis and related complications. Based on current data, the function of RBP4 as an adipokine exerting metabolic effects in glucose metabolism in humans remains uncertain and might be restricted to rodent models.
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PMID:Retinol-binding protein-4 in experimental and clinical metabolic disease. 1859 8

The metabolic syndrome is a constellation of metabolic risk factors and physical conditions that are accompanied by an enhanced propensity toward the development of type 2 diabetes, atherosclerosis, and cardiovascular disease. It presents a combination of atherosclerosis risk including atherogenic dyslipidemia, hypertension, elevated plasma glucose, hypercoagulability, and a proinflammatory state. The 2 major underlying risk factors for the metabolic syndrome are obesity and insulin resistance. Exacerbating factors are physical inactivity, advancing age, and endocrine and genetic factors. Associated hyperinsulinemia, hyperglycemia, and elevated adipokine levels (adipose cytokines) lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. In this 2-part series, the authors present an up-to-date and detailed systematic review of the literature on this important topic.
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PMID:The metabolic syndrome and cardiovascular disease: Part I. 1860 51

Inflammation is a key pathological process in the progression of atherosclerosis and type 2 diabetes. 12/15-lipoxygenase (12-LO), an enzyme involved in fatty acid metabolism, may contribute to inflammatory damage triggered by stressors such as obesity and insulin resistance. We hypothesized that mice lacking 12-LO are protected against inflammatory-mediated damage associated with a "western" diet. To test this hypothesis, age-matched male 12-LO knockout (12-LOKO) and wild-type C57BL/6 (B6) mice were fed either a standard chow or western diet and assessed for several inflammatory markers. Western-fed B6 mice showed expected reductions in glucose and insulin tolerance compared with chow-fed mice. In contrast, western-fed 12-LOKO mice maintained glucose and insulin tolerance similar to chow-fed mice. Circulating proinflammatory cytokines, tumor necrosis factor-alpha and interleukin-6, were increased in western B6 mice but not 12-LOKO mice, whereas the reported protective adipokine, adiponectin, was decreased only in western B6 mice. 12-LO activity was significantly elevated by western diet in islets from B6 mice. Islets from 12-LOKO mice did not show western-diet-induced islet hyperplasia or increases in caspase-3 apoptotic staining observed in western-fed B6 mice. Islets from 12-LOKO mice were also protected from reduced glucose-stimulated insulin secretion observed in islets from western-fed B6 mice. In visceral fat, macrophage numbers and monocyte chemoattractant protein-1 expression were elevated in western B6 mice but not 12-LOKO mice. These data suggest that 12-LO activation plays a role in western-diet-induced damage in visceral fat and islets. Inhibiting 12-LO may provide a new therapeutic approach to prevent inflammation-mediated metabolic consequences of excess fat intake.
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PMID:12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet. 1878 Jul 76

Obesity and inflammation are highly integrated processes in the pathogenesis of insulin resistance, diabetes, atherosclerosis, and non-alcoholic fatty liver disease. The evidence that obesity can be regarded as an inflammatory disease comes from numerous studies showing a moderate increase of circulating inflammatory factors in obese patients and the identification of different types of immune cells infiltrating the human adipose tissue. Obesity may induce a pro-inflammatory state, which can cause or worsen insulin resistance in adipose tissue, skeletal muscle, and liver. The causative factors of this inflammation process in obesity are not entirely understood, but adipose tissue seems to play an important role in the relationship between obesity and chronic inflammation. Increased infiltration of adipose tissue with immune cells could cause adipose tissue insulin resistance via autocrine and paracrine cytokine/adipokine signalling, which contributes to systemically decreased insulin sensitivity via endocrine signalling. On the other hand, obesity-induced inflammation could represent a compensatory mechanism for increased adipose tissue turnover in obese states, which might protect obese individuals against deleterious effects of fat accumulation. A better understanding of the mechanisms and molecular components of obesity induced inflammatory response might lead to identifying novel therapeutic targets to prevent obesity-related complications.
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PMID:The inflammatory process of adipose tissue. 1880 22


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