Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the effect of statin therapy (either alone or combined with ezetimibe) on the inhibition of cholesterol resorption and endothelial function by measuring forearm blood flow in male patients with the metabolic syndrome. Compared to 40 mg atorvastatin alone, combination therapy with 10 mg ezetimibe and 10 mg atorvastatin for 8 weeks resulted in significantly decreased total serum cholesterol and triglycerides levels (n = 14). Endothelium-dependent, acetylcholine-mediated vasodilation was significantly better with combination therapy (p < 0.05). In contrast, endothelium-independent forearm blood flow response to sodium nitroprusside was comparable in both groups. Our data suggest a more effective restoration of endothelial function with the statin/ezetimibe combination compared to statin monotherapy in patients with the metabolic syndrome.
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PMID:Endothelial function in the forearm circulation of patients with the metabolic syndrome--effect of different lipid-lowering regimens. 1644 9

These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR and 6 OZR) was measured after 2 min of muscle stimulation in the absence or presence of 1 microM SQ-29548 (TP antagonist). Additionally, arteriolar diameter (6 for each group) was measured after application of iloprost (prostacyclin analog; 0.28, 2.8, and 28 microM), arachidonic acid (10 microM), and sodium nitroprusside (0.1, 1, and 10 microM) in the absence or presence of 1 microM SQ-29548. A 10 microM concentration of adenosine was used to induce a maximal dilation. Basal diameters were not different between LZRs and OZRs. Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 microM SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs. Vasodilatory responses to iloprost and sodium nitroprusside (1 and 10 microM) were significantly reduced in OZR. Adenosine-mediated vasodilation was not different between groups. These results suggest that the impaired functional dilation in the OZR is due to an increased TP-mediated vasoconstriction and a decreased PGI2-induced vasodilation.
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PMID:Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome. 1616 9

Megalin is an endocytic receptor on the apical membranes of proximal tubule cells (PTC) in the kidney, and is involved in the reabsorption and metabolism of various proteins that have been filtered by glomeruli. Patients with diabetes, especially type 2 diabetes, or metabolic syndrome are likely to have elevated serum levels of advanced glycation end products, liver-type fatty acid binding protein, angiotensin II, insulin and leptin, and renal metabolism of these proteins is potentially overloaded. Some of these proteins are themselves nephrotoxic, while others are carriers of nephrotoxic molecules. Megalin is involved in the proximal tubular uptake of these proteins. We hypothesize that megalin-mediated metabolic overload in PTC leads to compensatory cellular hypertrophy and sustained Na+ reabsorption, causing systemic hypertension and glomerular hyperfiltration via tubuloglomerular feedback, and named this as 'protein metabolic overload hypothesis'. Impaired metabolism of bioactive proteins such as angiotensin II and insulin in PTC may enhance hypertrophy of PTC and/or Na+ reabsorption. Sleep apnoea syndrome, a frequent complication of diabetes and metabolic syndrome, may cause renal hypoxia and result in relative overload of protein metabolism in the kidneys. The development of strategies to identify patients with diabetes or metabolic syndrome who are at high risk for renal metabolic overload would allow intensive treatment of these patients in an effort to prevent the development of nephropathy. Further studies on the intracellular molecular signalling associated with megalin-mediated metabolic pathways may lead to the development of novel strategies for the treatment of nephropathies related to diabetes and metabolic syndrome.
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PMID:Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis. 1617 84

Metabolic syndrome is a cluster of metabolic abnormalities, including hypertension, hyperlipidemia, hyperinsulinemia, glucose intolerance and obesity. In such lifestyle-related diseases, impairment of nitric oxide (NO) production or bioactivity has been reported to lead to the development of atherogenic vascular diseases. Therefore, in the present study we investigated changes in the NO/cyclic guanosine monophosphate (cGMP) system in aortas of SHR/NDmcr-cp (cp/cp) rats (SHR-cp), a model of the metabolic syndrome. In aortas of SHR-cp, endothelium-dependent relaxations induced by acetylcholine and endothelium-independent relaxations induced by sodium nitroprusside were significantly impaired in comparison with Wistar-Kyoto rats. Furthermore, protein levels of soluble guanylyl cyclase and cGMP levels induced by sodium nitroprusside were significantly decreased. In contrast, protein levels of endothelium NO synthase and cGMP levels induced by acetylcholine were significantly increased, and plasma NO2 plus NO3 levels were also increased. The levels of lipid peroxide in plasma and the contents of 3-nitrotyrosine, a biomarker of peroxynitrite, in aortas were markedly increased. These findings indicate that in the aortas of SHR-cp, NO production from the endothelium is augmented, although the NO-induced relaxation response is impaired. Enhanced NO production may be a compensatory response to a variety of factors, including increases in oxidative stress.
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PMID:Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome. 1618 78

Increased levels of uric acid are associated with cardiovascular disease and the metabolic syndrome. They may predict clinical outcomes and also the onset of hypertension, though it is less clear that hyperuricaemia can be regarded as an independent risk factor given its clustering with other well-recognised factors. Uric acid may increase as a result of pathophysiological processes such as impaired renal sodium handling but may also contribute to renal and vascular damage, particularly endothelial dysfunction. It is notable that the synthesis of uric acid may be associated with the generation of reactive oxygen species if the enzyme xanthine oxidorectase is converted to the oxidase, as may occur in ischaemia. It has been suggested that uric acid may play a role in the pathogenesis of early-onset hypertension but evidence for this is limited. There is also very limited data to suggest that in some circumstances lowering uric acid can lower blood pressure. In the metabolic syndrome, the presence of elevated uric acid concentrations is closely associated with raised triglyceride levels, for reasons that have not been clearly defined. It remains to be seen whether uric acid could or should be considered a specific therapeutic target in cardiovascular disease and especially in hypertension and if so what should be the optimal pharmacological approach to lowering serum urate levels.
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PMID:Uric acid and hypertension. 1637 35

Coronary heart disease (CHD) morbidity and mortality are more prevalent in Blacks than Whites in the United States. Most studies evaluate the dietary intake and health of Black Americans as one group and do not consider possible differences among ethnic subgroups within the U.S. Black population. We used data from NHANES III to assess whether dietary intake, CHD risk factors, and predicted 10-y risk of CHD differed between non-Hispanic Black adults born in the United States (NHB-US), and non-Hispanic and Hispanic Black adults born outside of the United States (NHB-non US, HB-non US). Data were provided from single 24-h dietary recalls, biochemical measures, the medical examination, and self-reported responses to survey questions. NHB-US had higher intakes of energy, fat, protein, meat, added sugars, and sodium, and lower intakes of fruits, fiber, and most micronutrients. NHB-US also had higher predicted 10-y risk of developing CHD (5.8%) than NHB-non US (3.7%, P<0.001) or HB-non US (4.7%, P=0.017). Both immigrant groups had better CHD risk profiles and lower proportions of persons with metabolic syndrome and other CHD-related conditions. Our findings show differences in dietary intake and risk of CHD and related health conditions among ethnic subgroups of Blacks living in the United States. Future studies of diet and health should consider cultural differences within the Black population to better understand and reduce overall health disparities in the United States.
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PMID:Dietary intake and risk of coronary heart disease differ among ethnic subgroups of black Americans. 1642 26

Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARgamma is the most extensively studied amongst the three subtypes (alpha, delta and gamma). This receptor is a key modulator of lipid and glucose homeostasis and is predominantly expressed in adipose tissue. Expression of PPARgamma is also found in non-adipose tissues including heart, kidney, spleen, and interestingly, in all relevant components of the vasculature: endothelial and smooth muscle cells. These receptors may therefore also play a role in the regulation of vascular tone and blood pressure. Genetic variants of PPARgamma have also been associated with features of the metabolic syndrome, including obesity and increased blood pressure. The discovery of synthetic ligands for PPARgamma, the Thiazolidinediones (TZDs) has greatly enhanced our understanding of their ligand dependent activation and more importantly their role in vascular pathobiology. Approximately 10 years ago, serendipitous animal experiments demonstrated that despite causing sodium retention, the TZDs actually lowered blood pressure. This review will highlight the role of TZDs in various models of hypertension and discuss their potential role in the management of obesity-related hypertension.
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PMID:Can PPARgamma agonists have a role in the management of obesity-related hypertension? 1671 64

Obesity is frequently accompanied by insulin resistance, type II diabetes, hypertension and atherosclerosis, a cluster of pathologies that are the major components of the metabolic syndrome. Obesity is a known cause for renal dysfunction that leads to two major renal pathologies: hypertension and glomerular and tubulointerstitial injury. Peroxizome proliferator activated receptors (PPARs) are transcription factors belonging to the nuclear hormone receptor superfamily with important functions in the regulation of metabolism. The role of PPARgamma isoforms in adipogenesis and vascular inflammation associated to obesity has been vastly studied and is well recognized, albeit not completely mechanistically understood. Also, the effect of various PPARgamma agonists on blood pressure reduction in different forms of hypertension, including obesity related hypertension has been reported, but the mechanisms involved are only beginning to be studied. Even less clear is the concurrent beneficial effect of PPARgamma agonists thiazolinendiones (TZD) on blood pressure reduction in different forms of hypertension and, at the same time, in some cases, the significant water retention leading to edema and heart failure. The occurrence of both these apparently opposite effects on the renal water and sodium handling suggests a complex role of PPARgamma in the kidney that is likely related to the metabolic state. Also, PPARgamma activation leads to a reduction in mesangial cell proliferation while stimulating apoptosis. TZD treatment reduces albuminuria in obese and diabetic humans and rodent models suggesting protective effects against renal tubuloglomerular injury. The focus of this review is to present and critically discuss the recent findings on the roles of PPARgamma in the kidney in direct relation to renal function and renal injury in obesity and obesity-initiated diabetes.
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PMID:The complex role of PPARgamma in renal dysfunction in obesity: managing a Janus-faced receptor. 1671 56

The metabolic syndrome is a cluster of disturbances such as type 2 diabetes mellitus, hypertension, central obesity, dyslipidemia, and others for which insulin resistance and compensatory hyperinsulinemia have been proposed to be the underlying disorders. Several possible mechanisms linking insulin resistance and compensatory hyperinsulinemia with hypertension have been described, such as renal sodium reabsorption enhancement, sympathetic nervous system activation, and blunted insulin-mediated vasodilation caused by endothelial dysfunction. Peroxisome proliferator-activated receptors-gamma agonists or thiazolidinediones (TZD) are a class of agents for the treatment of type 2 diabetes mellitus that act through improvement of insulin sensitivity. In parallel to their antihyperglycemic action, these drugs were found to exert beneficial effects on other components of the metabolic syndrome. For example all TZD have been shown to reduce blood pressure (BP) levels in both animal and human studies. In addition a considerable number of in vitro and in vivo studies report actions of TZD on the cardiovascular system that could explain this blood pressure-lowering effect of TZD, such as restoration of blunted endothelium-mediated vasodilation, attenuation of sympathetic overactivity, inhibition of intracellular Ca(2+) increase, and proliferation of vascular smooth muscle cells and others. This review summarizes the current evidence about these actions of TZD that could positively influence BP, representing possible mechanisms of BP amelioration.
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PMID:Actions of peroxisome proliferator-activated receptors-gamma agonists explaining a possible blood pressure-lowering effect. 1673 40

Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese condition the prediabetic metabolic syndrome is caused by TNF-alpha overexpression. To test this, we measured endothelium-dependent (acetylcholine) and -independent vasodilation (sodium nitroprusside) of isolated, pressurized coronary small arteries from lean control and Zucker obese fatty (ZOF, a model of prediabetic metabolic syndrome) rats. In ZOF rats, dilation to ACh was blunted compared with lean rats, but sodium nitroprusside-induced dilation was comparable. Superoxide (O2*-) generation was elevated in vessels from ZOF rats compared with lean rats, and administration of the O2*- scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti-TNF-alpha restored endothelium-dependent dilation in the ZOF rats. Real-time PCR and Western blotting revealed that mRNA and protein of TNF-alpha were higher in ZOF rats than that in lean rats, whereas eNOS protein levels were reduced in the ZOF versus lean rats. Immunostaining showed that TNF-alpha in ZOF rat heart is localized in endothelial cells and vascular smooth muscle cells. Expression of NAD(P)H subunits p22 and p40-phox were elevated in ZOF compared with lean animals. Administration of TNF-alpha more than 3 days also induced expression of these NAD(P)H subunits and abrogated endothelium-dependent dilation. In conclusion, the results demonstrate the endothelial dysfunction occurring in the metabolic syndrome is the result of effects of the inflammatory cytokine TNF-alpha and subsequent production of O2*-.
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PMID:Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome. 1674 Nov 60


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