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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II is known to inhibit the insulin-signaling pathway. On the other hand, insulin causes activation of the cardiovascular renin-angiotensin system in both cardiac cells and vascular cells(smooth muscle cells and endothelial cells). Insulin-activated tissue renin-angiotensin system leads to increased cell growth and contributes to cardiac hypertrophy and atherosclerosis. The fact that agents that inhibit the renin-angiotensin system also block insulin-mediated renin-angiotensin system expression and cell growth reinforces the potential implication of a cardiovascular insulin-renin-angiotensin system pathway. This review examines the mechanisms that connect systemic insulin resistance to the cardiovascular complications in the metabolic syndrome, especially the relation between insulin-signaling pathway and angiotensin.
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PMID:[Role of angiotensin in the metabolic syndrome and cardiovascular complications]. 1239 81

Gender-specific differences in the incidence of cardiovascular disease have long been known, and estrogens have been considered to be responsible for this dissimilarity. Recently, the steep increase in cardiovascular risk in the no longer fertile woman has become evident. The postmenopausal metabolic syndrome is very frequent, with obesity, insulin resistance, and hyperinsulinemia, which convey increased sodium reabsorption, stimulation of the sympathetic nervous system, and smooth muscle growth. The clinical corollary of these overall changes is hypertension. Gender differences in components of the renin-angiotensin system have been shown to exist, and may play a central role in blood pressure control. In normotensive populations, plasma renin activity is significantly higher in men than in women, and is higher in postmenopausal versus premenopausal women. Two angiotensin-converting enzyme inhibitors, ramipril and moexipril, have undergone trials aimed specifically at older people with cardiovascular risk and with postmenopausal hypertension, and could be the first therapeutic choice. However, a comprehensive treatment should include nonpharmacologic measures with strong emphasis on weight normalization and regular physical activity, prevention of osteoporosis, as well as decisions on the use of estrogen replacement therapy and treatment of the menopausal metabolic syndrome. Finally, education of both patients and physicians on the nature and prognosis of untreated hypertension is crucial.
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PMID:Systemic hypertension in postmenopausal women: a clinical approach. 1241 76

Obesity, hypertension, and their co-morbid conditions such as diabetes mellitus and cardiovascular disease are major public health issues. This article reviews research that links hypertension and obesity, particularly the android obesity pattern that characterizes the metabolic syndrome. The article focuses on the relationships between hypertension, obesity, and the renin-angiotensin system (RAS). It explores new understandings about the RAS and the connections between RAS overactivity, hypertension, and obesity. Also discussed are lines of evidence that show that elevated visceral fat levels contribute to renin-angiotensin overactivity and that RAS overactivity contributes to the development of obesity. The bidirectional nature of the obesity-RAS relationship is discussed.
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PMID:Hypertension, obesity, and the renin-angiotensin system: a tale of tight associations. 1258 60

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.
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PMID:The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome? 1267 68

The obesity epidemic is driving metabolic (insulin resistance) syndrome-related health problems including an approximately threefold increased coronary heart disease risk. Sympathetic hyperfunction may participate in the pathogenesis and complications of the metabolic syndrome including higher blood pressure, a more active renin-angiotensin system, insulin resistance, faster heart rates, and excess cardiovascular disease including sudden death. Possible factors augmenting sympathetic activation in the metabolic syndrome include alterations of insulin, leptin, nonesterified fatty acids (NEFAs), cytokines, tri-iodothyronine, eicosanoids, sleep apnea, nitric oxide, endorphins, and neuropeptide Y. Of note, high plasma NEFAs are a risk factor for hypertension and sudden death. In short-term human studies, NEFAs can raise blood pressure, heart rate, and a(1)-adrenoceptor vasoreactivity, while reducing baroreflex sensitivity, endothelium-dependent vasodilatation, and vascular compliance. Efforts to further identify the mechanisms and consequences of sympathetic dysfunction in the metabolic syndrome may provide insights for therapeutic advances to ameliorate the excess cardiovascular risk and adverse outcomes.
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PMID:Insulin resistance and the sympathetic nervous system. 1272 58

Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The long-term hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II-mediated hypertension. Taken together, our findings suggest that overexpression of 11beta-HSD1 in fat is sufficient to cause salt-sensitive hypertension mediated by an activated RAS. The potential role of adipose 11beta-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder.
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PMID:Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. 1284 62

The prognosis for patients who suffer myocardial infarctions (MIs) is poor, with 22% of male and 46% of female survivors being disabled by heart failure within 6 years. Many well-established risk factors for increased morbidity and mortality post-MI are closely linked to the metabolic syndrome and associated with over-activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. Results from numerous large-scale clinical endpoint trials have shown that blocking the deleterious effects of these systems with either an angiotensin-converting enzyme inhibitor or a beta-adrenoceptor antagonist significantly reduces the risk of mortality and cardiovascular events in post-MI patients. Results from 1 recent study of the beta-blocker, carvedilol, have shown further that these benefits extend to high-risk patients with either diabetes or hypertension.
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PMID:Diabetes, hypertension, and renal insufficiency in post-myocardial infarction cardiovascular risk. 1456 32

Obstructive sleep apnoea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension. Although the association between OSA and the metabolic syndrome tends to confound studies of the independent effects of OSA on vascular disease, recent evidences from basic science to epidemiological and clinical studies suggest that OSA may add worsening pathophysiological conditions to obesity. OSA contributes to the imbalance between vasodilators and vasoconstrictors, in particular through oxidative stress-dependent catabolism of nitric oxide, increased sympathetic nerve activity, enhanced renin-angiotensin system activity and endothelin synthesis. Additionally, several recent studies suggest that OSA may be a circumstance favouring central and vascular resistance to leptin. The beneficial effects of this hormone in normal subjects, are lost during endothelial dysfunction and OSA. Moreover, high leptin concentrations, within a range observed during OSA, display adverse effects on endothelial function and vascular physiology. Through of a yet unknown mechanism, OSA per se accounts for part of the elevated serum leptin concentration reported in patients. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnoea and the ensuing acute hemodynamic changes during sleep. Accordingly, vasopressor mediators and leptin concentration are shifted toward normal values by CPAP. Thus, in addition to this effective therapy, evaluation of specific strategies targeting leptin sensitivity and vasopressor mediators may open novel perspectives for treatment of OSA and its associated end-organ damages.
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PMID:[Effect of sleep apnea syndrome on the vascular endothelium]. 1464 10

Concentrations of plasminogen activator inhibitor-1 (PAI-1) are elevated beginning at the stage of impaired glucose tolerance and continuing through the development of diabetes mellitus and the metabolic syndrome. Evolving evidence of the central role of PAI-1 in mediating fibrosis and thrombosis increasingly supports the theory that it is a significant risk factor for macrovascular complications and cardiovascular disease, particularly in patients with diabetes. Several clinical studies have demonstrated a strong correlation between circulating PAI-1 levels and cardiovascular events and mortality. With the potentially severe effects of elevated PAI-1 levels becoming evident, there is increased interest in developing therapies targeted at reducing PAI-1 expression or circulating concentrations. Thus far, weight loss, inhibitors of the renin-angiotensin system, and insulin sensitization through use of thiazolidinediones (TZDs) appear to be the most promising strategies for managing elevated PAI-1 levels. Of these, TZD therapy is the only one that provides the benefits of both long-term glycemic control and improved cardiovascular risk profile. This article reviews the regulation of PAI-1, its activity in various disease states, and available treatment options.
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PMID:Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease. 1467 68

The prevalence of chronic kidney disease (CKD) is on the rise in all ethnic groups. This is because of the increased prevalence of obesity, diabetes mellitus, the metabolic syndrome, and the inadequate control of elevated blood pressure and other cardiovascular-renal risk factors, especially in ethnic minority populations. The implications of the aforementioned trends in risk factor prevalence and control are profound. Moreover, these trends negatively impact patient quality of life and place an enormous financial burden on the health care system for the provision of care to patients with CKD, end-stage renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost importance to devise strategies that prevent kidney disease and delay progressive loss of kidney function in persons with CKD. Proven strategies include pharmacological interventions that lower blood pressure to less than target levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and reducing urinary protein excretion. It is also possible, although yet unproven, that correction of anemia and aggressive treatment of dyslipidemia may forestall the loss of kidney function. In general, ethnic minorities are underrepresented in most large trials. Recently, a few outcome clinical trials in blacks have reinforced the lessons of kidney function preservation already learned in nonblack populations. That is, the reversible risk factors for CKD appear to be virtually identical and, at least in nondiabetic CKD, pharmacological targeting of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers preserves kidney function better than non-RAAS blood pressure-lowering regimens, especially when significant proteinuria exists. Although more CKD studies in ethnic minorities are needed, until they become available, the best available evidence from the existing clinical trial database should be applied to minorities with CKD-even when specific data are not available for a specific racial or ethnic group. Why this approach? First, there are no known unique risk factors for kidney disease in any ethnic group. Second, poor control of reversible risk factors for CKD is universal, particularly in blacks and other ethnic minorities. Thus, it is logical to predict that more efficient use of strategies proven to forestall loss of kidney function will reduce the excess of CKD and ESRD in ethnic minorities relative to non-minority populations. However, medical-based strategies alone are probably not enough. The global epidemic of obesity will fuel the growing population of persons, especially among ethnic minorities, with diabetes, the main cause of CKD, ESRD, and CVD. The obesity and diabetes epidemics are unlikely to abate without innovative and ultimately effective public health approaches.
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PMID:Pharmacological strategies for kidney function preservation: are there differences by ethnicity? 1473 May 36


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