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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-eight obese children and adolescents were investigated for a possible relation between cholesterol and markers of platelet activation, endothelial cell dysfunction, and activation of the coagulation system. Soluble P-selectin, von Willebrand factor antigen (vWf-Ag), D-dimer, and prothrombin fragment 1 + 2 (F1 + 2) were determined by enzyme-linked immunosorbent assays, and factor VIII coagulant activity (VIIIc) was measured by means of one-stage clotting assay. Cholesterol correlated significantly with log P-selectin (r = 0.43, P = 0.003) and log D-dimer (r = 0.33, P = 0.02). Cholesterol did not correlate with vWf-Ag, factor VIIIc, and F1 + 2. Log P-selectin correlated significantly with log D-dimer (r = 0.42, P = 0.003), which remained significant after adjustment for cholesterol (P = 0.02). Log D-dimer correlated significantly with F1 + 2 (r = 0.38, P = 0.01). Our study demonstrates that, in obese children and adolescents, cholesterol is significantly associated with P-selectin and D-dimer, and suggests an unfavorable intercorrelation between metabolic and hemostatic risk factors for coronary heart disease in childhood obesity.
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PMID:Correlation between cholesterol, soluble P-selectin, and D-dimer in obese children and adolescents. 1113 54

Platelet activation is involved in the pathogenesis of atherosclerosis and venous thromboembolism, and might therefore be a possible link between the two entities. Prolactin and leptin have recently been recognized as potent co-activators of ADP-dependent platelet aggregation or P-selectin expression, and are therefore suspected as additional risk factors for both arterial and venous thrombosis. There are clinical situations that have a known association with higher prolactin or leptin levels (pregnancy, obesity or anti-psychotic therapy) and increased risk of thromboembolic events. We compared the impact of both hormones on platelet activation in vitro and in vivo, indicating that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. We have also demonstrated that prolactin levels are increased in so called idiopathic thrombosis, and that conversely, patients with prolactinoma have an increased frequency of thrombosis during the hyperprolactinemic state, in a retrospective analysis. Moreover, we have demonstrated increased prolactin values in stroke and myocardial infarction. Prospective studies have yet to be performed to give this theory its final confirmation. The involvement of hormonal factors in platelet aggregation and venous or arterial thrombosis may have important clinical implications such as for risk stratification of patients with venous and arterial thrombosis or new therapeutic options such as decreasing pro-coagulant hormone levels in certain risk situations.
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PMID:Co-activation of platelets by prolactin or leptin--pathophysiological findings and clinical implications. 1498 99

Hormones such as prolactin and leptin have recently been recognized as potent platelet aggregation co-activators, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. Clinical situations exist that are known to be associated with higher leptin and/or prolactin levels (obesity, pregnancy, prolactinomas and anti-psychotic therapy respectively) and increased venous thrombosis or atherosclerosis risk. Therefore, we compared the impact of both hormones on platelet activation in vitro and in vivo. First, we investigated platelet aggregation and P-selectin expression after stimulation with 1,000 mU/l prolactin or 100 ng/ml leptin in five healthy volunteers in vitro. Prolactin revealed significant higher levels of P-selectin expression and platelet aggregation than leptin in all subjects. We also compared the correlation of prolactin and leptin values with the P-selection expression on platelets. Previously, we detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in pregnant women, patients with pituitary tumours, and patients on anti-psychotic therapy. In contrast, leptin did not correlate with P-selectin expression in all subject groups investigated. However, leptin correlated with body mass index in the subjects investigated. Our data indicate that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. Moreover, our data suggest that the stronger effect of prolactin on ADP-stimulated platelet aggregation, compared to leptin, depends on higher stimulation of CD62p expression by prolactin.
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PMID:Differences in platelet activation by prolactin and leptin. 1530 27

Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.
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PMID:Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. 1550 18

Type 2 diabetes mellitus (DM) and the metabolic syndrome, both characterized by insulin resistance, are associated with an accelerated form of atherosclerotic vascular disease and poor outcomes following vascular interventions. These vascular effects are thought to stem from a heightened inflammatory environment and reduced bioavailability of nitric oxide (NO). To better understand this process, we characterized the vascular injury response in the obese Zucker rat by examining the expression of adhesion molecules, the recruitment of inflammatory cells, and the development of intimal hyperplasia. We also evaluated the ability of exogenous NO to inhibit the sequela of vascular injury in the metabolic syndrome. Obese and lean Zucker rats underwent carotid artery balloon injury. ICAM-1 and P-selectin expression were increased following injury in the obese animals compared with the lean rats. The obese rats also responded with increased macrophage infiltration of the vascular wall as well as increased neointima formation compared with their lean counterparts (intima/media = 0.91 vs. 0.52, P = 0.001). After adenovirus-mediated inducible NO synthase (iNOS) gene transfer, ICAM-1, P-selectin, inflammatory cell influx, and oxidized low-density lipoprotein (LDL) receptor expression were all markedly reduced versus injury alone. iNOS gene transfer also significantly inhibited proliferative activity (54% and 73%; P < 0.05) and neointima formation (53% and 67%; P < 0.05) in lean and obese animals, respectively. The vascular injury response in the face of obesity and the metabolic syndrome is associated with increased adhesion molecule expression, inflammatory cell infiltration, oxidized LDL receptor expression, and proliferation. iNOS gene transfer is able to effectively inhibit this heightened injury response and reduce neointima formation in this proinflammatory environment.
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PMID:Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome. 1573 83

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.
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PMID:Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study. 1600 61

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor that comprises the primary molecular target for thiazolidinedione (TZD) insulin-sensitizing drugs. Whilst expressed in many tissues in humans, its abundant expression in adipose tissue is believed to be the focal point through which TZDs regulate genes involved in glucose and lipid metabolism and via which these agents ultimately improve the hyperglycemia of type 2 diabetes. However, TZDs exhibit many additional properties, not least an array of effects which suggest a broad attack on the inflammatory process. Thus, TZDs have been shown to reduce plasma levels of the chemokine, monocyte chemotactic protein-1 (MCP-1), the anti-fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1), the endothelial cell adhesion molecules, e-selectin and inter-cellular adhesion molecule-1 (ICAM-1), the leucocyte-activating molecule, CD40L, and the tissue-remodeling enzyme, matrix metalloproteinase-9 (MMP-9). Further tangible evidence of a reduction by TZDs of systemic inflammation in patients with the classical metabolic syndrome stems from falls in the white blood cell count, P-selectin-positive platelets and in the acute-phase inflammatory proteins, C-reactive protein, serum amyloid A and fibrinogen. At the tissue level, TZDs improve vascular endothelial function, and reduce the rate of progression of intimal-medial thickening of the carotid artery and the microalbuminuria of type 2 diabetes. Further, TZDs have been shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis (NASH). In the case of the latter, a broad spectrum of TZD-related properties is visible. Here, these drugs improve insulin sensitivity for glucose metabolism, reduce hyperinsulinemia, hepatic steatosis, inflammation and fibrosis, and lower the circulating levels of liver transaminases (ALT, AST), alkaline phosphatase and gamma glutamyl transferase. These effects in humans are also well-supported by investigative animal and in vitro studies. The ameliorative effects on liver fibrosis are of particular interest since they suggest that TZDs are able to activate a program of corrective tissue-remodeling. The basis for this action may be partly an ability to inhibit matrix protein secretion by hepatic stellate cells. An analogous action has also been seen in kidney mesangial cells. In conclusion, TZDs are important new drugs, presently indicated for the treatment of type 2 diabetes but with a spectrum of properties which suggests their potential for treating a number of degenerative inflammatory diseases, including NASH. However, full-scale, long-term clinical trials are needed with TZDs to test their potential to treat NASH, not least because of the (hepatotoxic) legacy of the prototype TZD, troglitazone, but also in view of the escalating burden of liver disease which is accompanying the increasing global prevalence of clinical obesity and type 2 diabetes.
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PMID:Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection. 1619 19

Abnormal levels some of serum soluble adhesion molecules (ICAM-1, VICAM-1, E-selectin, P-selectin, L-selectin) have been detected in type 2 diabetic patients. There is some evidence that levels of soluble adhesion molecules depend on glycemic control, disturbances of lipid metabolism, obesity and insulin resistance. There is a few of clinical data till now, which have been suggested the significance role of adhesion molecules in pathogenesis of microangiopathy and macroangiopathy in type 2 diabetics. It is possible that in some cases measurement of serum adhesion molecules may be useful for predicting, early diagnosing prophylactic and monitoring of treatment of diabetic type 2 complications. We can modify serum levels of soluble adhesion molecules by nonpharmacologic and pharmacologic treatment.
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PMID:[Adhesion molecules in type 2 diabetes]. 1622 42

The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2alpha, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1alpha, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P < 0.05) in body mass index, all serum lipids and lipid ratios, fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2alpha, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1alpha, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may ameliorate novel coronary artery disease risk factors in men with metabolic syndrome factors before reversal of obesity.
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PMID:Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors. 1661 61

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p < 0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.
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PMID:Elevation of serum soluble E- and P-selectin in patients with hypertension is reversed by benidipine, a long-acting calcium channel blocker. 1655 75


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