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

HYPERTENSION-ASSOCIATED ABNORMALITIES THAT PROMOTE CORONARY DISEASE: Although antihypertensive treatment has been effective in reducing premature cardiovascular mortality, the effect on various organ-specific morbid events has been unequal; the effect is much more impressive on stroke reduction than on reduction of coronary events. A student of pathophysiology would have anticipated such an outcome since blood pressure elevation is only one of multiple abnormalities in hypertension. Even in its mildest form hypertension is associated with the metabolic syndrome of dyslipidemia/insulin resistance which is conducive to early atherosclerosis. A large proportion of patients also have increased sympathetic and decreased parasympathetic tone, a constellation conducive to arrhythmias and, ultimately, to sudden death. An elevated hematocrit is also found in a substantial proportion of male patients and excessive platelet aggregability has also been described in hypertension. These hematologic abnormalities are conducive to coronary thrombosis. Angiotensin II and norepinephrine, two of the most potent trophic hormones, are frequently elevated in hypertension. The effect of these hormones on the cardiac and vascular structure further increases the predilection for negative outcomes. Left ventricular hypertrophy is a potent risk factor of coronary mortality, congestive heart failure and sudden death. Vascular hypertrophy reduces the coronary reserve and at the level of skeletal muscles contributes to the evolution of the metabolic syndrome. ORGAN-SPECIFIC HYPERTENSION TREATMENT: Because of these abnormalities we are entering a new era of treatment in hypertension. Whereas an effective fall in blood pressure remains the main goal of treatment, differential effects of various antihypertensive agents on organ-specific morbidity are being actively explored. If this research proves that certain drugs have a specific advantage in defined subgroups of patients, clinical practice will change. It is reasonable to expect that in the next century we will witness a further improvement in the impact of antihypertensive treatment on public health.
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PMID:Coronary disease in hypertension: a new mosaic. 921 91

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

The metabolic syndrome is a worldwide epidemic, setting the stage for type 2 diabetes and its microvascular complications, and acceleration of macrovascular disease. Insulin resistance, hyperglycemia, dyslipidemia, hypertension, thrombotic disorders and adiposity define the metabolic syndrome and contribute to endothelial dysfunction and, subsequently, to accelerated atherosclerosis. Angiotensin II contributes to the development and progression of cardiovascular and renal endpoints and, as such, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors demonstrate a protective effect. Ligands for the peroxisome proliferator-activated receptor gamma (PPAR gamma), appear to impact favourably on atherosclerosis through both direct and indirect mechanisms. In humans, these ligands improve endothelial function, attenuate albuminuria and hypertension, and potentially prevent conversion of prediabetes to type 2 diabetes. Statins also have proven benefit in decreasing overall cardiovascular and stroke mortality and morbidity. The combination of angiotensin II blockade, statin therapy and PPAR gamma activation might emerge as an important global therapeutic strategy in the metabolic syndrome and diabetes. Further studies are needed to determine whether they have synergistic effects to protect the vasculature.
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PMID:Metabolic syndrome-interdependence of the cardiovascular and metabolic pathways. 1578 Aug 21

Hypertension commonly occurs as part of a genetically complex disorder of carbohydrate and lipid metabolism known as the metabolic syndrome. Most current antihypertensive drugs appear ineffective against the metabolic syndrome, which is a strong predictor of cardiovascular disease and death in affected patients. Angiotensin II can influence the activity of certain genes and cellular and biochemical pathways that may contribute to the pathogenesis of the metabolic syndrome. However, as a class, angiotensin II receptor blockers (ARBs) have proven only minimally to modestly effective in ameliorating the disturbances in carbohydrate and lipid metabolism that characterise the metabolic syndrome. Recent preclinical studies indicate that the ARB telmisartan acts as a selective peroxisome proliferators-activated receptor-gamma (PPARgamma) modulator when tested at concentrations that might be achievable with oral doses recommended for treatment of hypertension; this property does not appear to be shared by other ARBs. PPARgamma is a nuclear receptor that influences the expression of multiple genes involved in carbohydrate and lipid metabolism and is an attractive therapeutic target for the prevention and control of insulin resistance, type 2 diabetes and atherosclerosis. In cellular transactivation assays, telmisartan functioned as a partial agonist of PPARgamma and achieved 25-30% of maximal receptor activation attained with conventional PPARgamma ligands. Preclinical and clinical studies indicate that administration of telmisartan can improve carbohydrate and lipid metabolism without causing the side effects that accompany full PPARgamma activators. If the preliminary data are supported by the results of ongoing large-scale clinical studies, telmisartan could have a central role in the prevention and treatment of metabolic syndrome, diabetes and atherosclerosis.
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PMID:Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-gamma activator. 1586 21

Although catecholamine is a well-known classical hormone, its precise pathophysiological role remains obscure. Recently, growing evidence suggests that this hormone plays a causative role in several common diseases such as hypertension, diabetes, and dyslipidemia (metabolic syndrome). Thus, the discussion that follows will mainly focus on our data, including: 1) leptin as well Ang II subtype-2 receptor (AT2), assumed to be a key molecule for metabolic syndrome, much involved in regulating catecholamine synthesis and secretion. 2) Recent progress of pheochromocytoma (SDHX and Peptidergic Regulation). 3) Chromogranin A, as a possible marker for chronic sympatho-adrenal activities.
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PMID:[Recent progress of catecholamines--mainly focusing on metabolic syndrome]. 1629 41

Angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1) are expressed in both vascular and adipose tissues. Angiotensin II (AG II) has an adipogenic effect and increases PAI-1 expression. To evaluate the chronic effects of AG II type 1 receptor (AT(1)R) antagonism on adipose mass and PAI-1 expression in vascular and adipose tissues, losartan (30mg/kg/day) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, for 20 weeks. Adipose mass and regional fat distribution in the abdomen did not change after chronic AT(1)R antagonism in OLETF rats. AGT and PAI-1 mRNA expressions in adipose tissue of OLETF rats were significantly increased compared with Long-Evans Tokushima Otsuka (LETO) rats, the normal control. Chronic losartan therapy further increased the level of adipose AGT in OLETF rats, but did not affect the level of adipose PAI-1 mRNA. In contrast, aortic PAI-1 expression in OLETF rats was attenuated by chronic losartan therapy. Our results have two implications. First, adipose tissue may be an important source of AG II in metabolic syndrome even after chronic losartan therapy. Second, chronic AT(1)R antagonism with losartan causes differential effects on vascular and adipose PAI-1 expression.
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PMID:Chronic blockade of the angiotensin II receptor has a differential effect on adipose and vascular PAI-1 in OLETF rats. 1641 28

Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease (CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II (Ang II) type-1 receptor blocker (ARB) on the regulation of adipocytokines. Olmesartan, an ARB, significantly blunted the age- and body weight-associated falls in plasma adiponectin both in genetically and diet-induced obese mice, without affecting body weight, but had no effect on plasma adiponectin levels in lean mice. Olmesartan also ameliorated dysregulation of adipocytokines in obesity, such as tumor necrosis factor-alpha, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, and serum amyloid A3. Olmesartan significantly reduced reactive oxygen species originating from accumulated fat and attenuated the expression of nicotinamide adenine dinucleotide phospho hydrogenase oxidase subunits in adipose tissue. In cultured adipocytes, olmesartan acted as an antioxidant and improved adipocytokine dysregulation. Our results indicate that blockade of Ang II receptor ameliorates adipocytokine dysregulation and that such action is mediated, at least in part, by targeting oxidative stress in obese adipose tissue. Ang II signaling and subsequent oxidative stress in adipose tissue may be potential targets for the prevention of atherosclerotic cardiovascular disease in metabolic syndrome and also in metabolic syndrome-based CKD.
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PMID:Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. 1708 Jan 58

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

Excess body weight, high blood pressure, and insulin resistance together have been denominated the metabolic syndrome. In this review, we analyze the potential role of angiotensin II (Ang II) and reactive oxygen species in mediating inflammation in the metabolic syndrome. Ang II induces pro-inflammatory genes and other pro-inflammatory substances and increases oxidative stress that could damage endothelium, myocardium, and renal tissue. Activation of nuclear factor-kappaB and NAD(P)H oxidase are fundamental steps in these pro-inflammatory mechanisms in which intramitochondrial oxidative stress could play a critical role. This sequence of events might explain why reduction in Ang II synthesis by angiotensin-converting enzyme inhibitors (ACEIs) and Ang II type 1 (AT1) receptor blockers (ARBs) have a protective effect against cardiovascular disease.
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PMID:Inflammation and the metabolic syndrome: role of angiotensin II and oxidative stress. 1714 16

Precocious pubarche is the appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The most frequent etiology is idiopathic precocious adrenarche, suggested, after long-term follow-up, to be associated with metabolic syndrome. One of the factors involved in the genesis of precocious adrenarche is Angiotensin II (Ang II), which promotes cell proliferation and steroidogenesis through type 1 (AT1) and type 2 (AT2) receptors. In order to study Ang II receptors mutations, 50 children with idiopathic precocious adrenarche were evaluated and compared to a control group of normal individuals. Mutations were not detected in the AGTR1 and AGTR2 genes; however, two polymorphisms were identified in the AGTR1 gene: the C573T (exon 5) and the A1166C (3' untranslated region). The polymorphic allele T573 was found in 35% of the patients and 38% of controls. The polymorphic allele C1166 was present in 24% of the patients and 26% of controls. There was no statistical difference between groups. There was also no correlation between the polymorphisms and clinical and laboratory findings, as well as their family history of metabolic syndrome.
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PMID:[Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche]. 1716 Feb 13


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