UMLS:C0948265 - FACTA Search

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

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.
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PMID:The renin angiotensin system as a therapeutic target to prevent diabetes and its complications. 1569 45

It is well recognised that the metabolic syndrome, a constellation of risk factors including obesity, hypertension, insulin resistance and dyslipidaemia, is associated with an increased risk of cardiovascular complications and the development of Type 2 diabetes. Consequently, timely identification and management of all components of the metabolic syndrome is warranted. In particular, guidelines have emphasised the importance of targeting elevated blood pressure (BP) and dyslipidaemia as a method of reducing global cardiovascular risk. Findings from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial show that the angiotensin receptor blocker, valsartan, reduces cardiovascular events and the development of Type 2 diabetes in high-risk individuals. This profile is being further explored in the ongoing Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Given the potential advantages to patients and physicians of tackling more than one of the components of the metabolic syndrome, antihypertensive agents such as valsartan would appear to be and important addition to the management of vulnerable patients at high risk of cardiovascular events.
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PMID:Angiotensin receptor blockers: Cardiovascular protection in the metabolic syndrome. 1698 30

Clinical and experimental evidence suggest that the renin-angiotensin system (RAS) plays a role in metabolic syndrome. Adipogenesis is suggested to modulate obesity and obesity-related consequences, such as metabolic syndrome. Although mesenchymal stem cells (MSCs) are a major source of adipocyte generation, the influence of RAS on MSC differentiation to adipocyte is unknown. We evaluated the expression of endogenous RAS in human MSCs during its differentiation to adipocytes and studied the effects of angiotensin II (Ang II), Ang II type 1 receptor blocker Valsartan, and type 2 (AT(2)) receptor blocker PD123319. Our data showed that differentiation was associated with an increase in cellular renin and AT(2) receptor expression and a concomitant decrease in angiotensinogen and angiotensin-converting enzyme expression. The net effect is an increase in endogenous cellular angiotensin II production. Incubation with Ang II (exogenous) inhibited adipogenesis. Combined treatment of exogenous Ang II and Valsartan further inhibited adipogenesis, whereas combined treatment of Ang II and PD123319 completely abolished the inhibition of adipogenesis, suggesting an important role for the AT(2) receptor. Blockade of endogenous angiotensin II effect by incubation with Valsartan alone inhibited adipogenesis, whereas PD123319 alone promoted adipogenesis, confirming the data using exogenous Ang II. The combination of Valsartan and PD123319 had no net effect. Our data demonstrate an important role of the expression of the local RAS in the regulation of human MSC differentiation to adipocytes. Elucidation of the molecular mechanism should provide important insight into the pathophysiology of the metabolic syndrome and the development of future therapeutics.
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PMID:Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes. 1706 May 13

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are thought to possess cardioprotective, cerebroprotective, and nephroprotective properties. Both classes of agents can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with angiotensin-converting enzyme inhibitors in patients with coronary artery disease, but no such data are scarce with angiotensin receptor blockers (Valsartan in Acute Myocardial Infarction study). Both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. These drugs (especially angiotensin receptor blockers) may successfully prevent atrial fibrillation and play a protective role in metabolic syndrome. In some clinical settings, combined therapy angiotensin-converting enzyme inhibitors with angiotensin receptor blocker (double blockade of the renin-angiotensin- aldosterone system) may appear the most effective.
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PMID:On target to dual block RAS? 1914 53

Valsartan is a nonpeptide angiotensin receptor antagonist that selectively blocks the binding of angiotensin II to the angiotensin II type 1 receptor. The efficacy, tolerability and safety of valsartan have been demonstrated in large-scale studies in hypertension, heart failure (HF) and post-myocardial infarction (MI). This review focuses on what was learned from the valsartan clinical research programme and other comparative trials published from 1997 to the present. Many studies have demonstrated the efficacy of valsartan in lowering blood pressure (BP) in a variety of patient populations (including elderly, women, children, obese patients, patients with diabetes mellitus, patients with chronic kidney disease [CKD], patients at high risk of cardiovascular [CV] disease, African Americans, Hispanic Americans and Asians) and in improving outcomes in CV disease and CKD. In hypertension, valsartan exhibits dose-dependent efficacy in reducing both systolic and diastolic BP over the once-daily dose range of 80-320 mg; doses as high as 640 mg/day have been studied and found to be efficacious and safe. BP control can be enhanced with a more consistent 24-hour BP-lowering profile by using single-pill, fixed-dose combination therapy with valsartan plus hydrochlorothiazide (HCTZ). The cardioprotective benefits of valsartan have been demonstrated in large-scale outcome trials and include significant reductions in CV morbidity and mortality in HF, following MI, and in patients with co-morbid hypertension and coronary artery disease and/or HF; reductions in HF hospitalizations; and reductions in the incidence of stroke. The magnitude of these effects is comparable with that demonstrated with angiotensin-converting enzyme (ACE) inhibitors; however, valsartan has a more favourable tolerability profile, with a significantly lower incidence of cough and only rare reports of angio-oedema, both class effects of ACE inhibitor use. Consistent with its angiotensin receptor-blocking effects, valsartan also reduces circulating levels of biochemical markers that are associated with angiotensin II-mediated endothelial dysfunction and CV risk (e.g. high-sensitivity C-reactive protein or oxidized low-density lipoprotein). Improvements in CKD with valsartan include statistically and clinically meaningful reductions in urinary albumin and protein excretion in patients with type 2 diabetes and in nondiabetic patients with CKD. In short-term studies, valsartan has improved or stabilized various indices of metabolic function in at-risk patients, including those with co-morbid hypertension, obesity and/or metabolic syndrome. Because of this, valsartan is being prospectively investigated for its ability to reduce the incidence of new-onset diabetes and provide cardioprotection in patients with impaired glucose tolerance. Valsartan and valsartan/HCTZ are well tolerated. In clinical trials, adverse events during valsartan treatment were similar to those occurring with placebo. The combination of valsartan/HCTZ was better tolerated than HCTZ alone. Valsartan is administered once daily for hypertension; doses are usually taken upon awakening. In patients with HF or MI, valsartan is administered twice daily.
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PMID:Valsartan: more than a decade of experience. 1991 55

Obesity, hypertension, cardiovascular disease, and inflammation are closely associated with the rising incidence of diabetes mellitus. One pharmacological target that may have significant potential to lower the risk of obesity-related diseases is the angiotensin type 1 receptor (AT1R). We examined the hypothesis that the AT1R blocker valsartan reduces the metabolic consequences and inflammatory effects of a high-fat (Western) diet in mice. C57BL/6J mice were treated by oral gavage with 10 mg/kg per day of valsartan or vehicle and placed on either a standard chow or Western diet for 12 weeks. Western diet-fed mice given valsartan had improved glucose tolerance, reduced fasting blood glucose levels, and reduced serum insulin levels compared with mice fed a Western diet alone. Valsartan treatment also blocked Western diet-induced increases in serum levels of the proinflammatory cytokines interferon-gamma and monocyte chemotactic protein 1. In the pancreatic islets, valsartan enhanced mitochondrial function and prevented Western diet-induced decreases in glucose-stimulated insulin secretion. In adipose tissue, valsartan reduced Western diet-induced macrophage infiltration and expression of macrophage-derived monocyte chemotactic protein 1. In isolated adipocytes, valsartan treatment blocked or attenuated Western diet-induced changes in expression of several key inflammatory signals: interleukin 12p40, interleukin 12p35, tumor necrosis factor-alpha, interferon-gamma, adiponectin, platelet 12-lipoxygenase, collagen 6, inducible NO synthase, and AT1R. Our findings indicate that AT1R blockade with valsartan attenuated several deleterious effects of the Western diet at the systemic and local levels in islets and adipose tissue. This study suggests that AT1R blockers provide additional therapeutic benefits in the metabolic syndrome and other obesity-related disorders beyond lowering blood pressure.
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PMID:Valsartan protects pancreatic islets and adipose tissue from the inflammatory and metabolic consequences of a high-fat diet in mice. 2105 93

The Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is exploring two pharmacological strategies (nateglinide and valsartan, both alone and in combination) in the prevention of overt diabetes mellitus (DM) and the reduction of cardiovascular disease (CVD) in subjects at high risk for these events. In this analysis, we provide baseline characteristics of the randomized NAVIGATOR study population and contrast them with those from other trials of DM prevention. Key eligibility criteria include impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), a history of CVD (in patients aged > or =50 years), and > or =1 cardiovascular risk factor (in patients aged > or =55 years). Baseline demographic characteristics, laboratory findings, cardiovascular risk factors, CVD history, and medication use are described and compared with other trials of DM prevention. The full analysis set of subjects (N = 9306) showed a clustering of risk factors consistent with the metabolic syndrome: high rates of hypertension (77.5%), dyslipidemia (44.7%), increased waist circumference (101.0 cm), and high body mass index (BMI) (47.5% with BMI > or =30 kg/m(2)). A minority of patients had a history of CVD (24.3%); of these, 11.7% had a history of myocardial infarction and most of the remainder had evidence of coronary artery disease. Subjects also had elevated blood pressure (BP) (predominantly systolic) (139.7/82.6 mm Hg), increased serum low-density lipoproteins cholesterol levels (3.27 mmol/L), and borderline elevation of triglyceride levels (1.97 mmol/L). Demographic data, BP, and lipid profiles in NAVIGATOR were similar to those of previous DM prevention trials, which were also based largely on meeting criteria for IGT. Medication use at baseline among NAVIGATOR subjects, which frequently included aspirin, beta-blockers, calcium channel blockers, diuretics, and lipid-lowering agents, reflects enhanced CVD risk. However, little prescribing of renin-angiotensin-aldosterone system blockers was observed, likely due to protocol exclusion criteria. In conclusion, the NAVIGATOR study comprises prediabetic subjects who typically have concurrent BP and metabolic disturbances and an enhanced risk of CVD, and are thus at higher risk for cardiovascular events than subjects in previous DM prevention trials.
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PMID:Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. 2018 89

The presence of metabolic syndrome (Mets) increases the risk for cardiovascular disease. There is a significant correlation between the levels of urinary albumin to creatinine ratio (UACR) and high-sensitive C-reactive peptide (hs-CRP), and accumulation of each Mets component. Increasing evidence has shown the importance of blockade of renin-angiotensin-systems (RAS) for reducing urinary albumin excretion and hs-CRP levels in Mets patients. However, the impact of RAS blockade on these effects in hypertensive (HT) Mets patients without diabetes mellitus (DM) has not been evaluated. We prospectively measured the levels of UACR and hs-CRP in 153 HT patients with and without Mets. Body weight; waist circumference; presence of dyslipidemia and DM, and levels of HOMA-R, UACR, and hs-CRP were significantly higher in HT patients with Mets than in those without Mets. After we treated these Mets patients with valsartan for 6 months, blood pressure (BP), UACR, and hs-CRP were decreased, whereas body weight, HOMR-R, and the lipid profile were not changed. In HT Mets patients without DM, 6 months after valsartan administration, levels of UACR and hs-CRP were also significantly decreased by 37.8% (-9.0-56.5%, p < 0.05) and 23.6% (-28.7-73.4%, p < 0.05), respectively. However, the percentage change of UACR and hs-CRP was not correlated with the reduction in BP. Valsartan administration lowered increased levels of chronic inflammation in both HT Mets patients with DM and in those without DM. These results indicate that the anti-inflammatory properties of valsartan might also have beneficial effects in Mets patients without DM.
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PMID:Suppressive effects of valsartan on microalbuminuria and CRP in patients with metabolic syndrome (Val-Mets). 2126 62

To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues.
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PMID:[Effect of Astragali Radix in improving early renal damage in metabolic syndrome rats through ACE2/Mas pathway]. 2707 Dec 65