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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome and type 2 diabetes are associated with endothelial activation (and thus with inflammatory processes leading to atherosclerosis), but the mechanisms that underlie these associations are not fully understood. Endothelial intercellular adhesion molecule (ICAM)-1 plays an important role in the recruitment of immune cells during the development of atherosclerotic plaque and is a marker of inflammatory disease. We performed bivariate quantitative genetic analyses to estimate genetic and environmental correlations between circulating ICAM-1 concentration and 17 phenotypes associated with the metabolic syndrome. Our study population comprised 428 adults in 20 extended Mexican-American families from the San Antonio Family Heart Study (SAFHS). Circulating ICAM-1 concentration is heritable (h(2) = 0.56). ICAM-1 concentration showed significant positive genetic correlations (range 0.32-0.52, P < 0.05) with fasting insulin, insulin 2 h after oral glucose challenge, homeostasis model assessment of insulin resistance, BMI, waist circumference, and leptin concentration; negative genetic correlation with HDL3 cholesterol concentration; and negative environmental correlation with adiponectin concentration. Significant genetic correlations were not found between ICAM-1 and fasting or 2-h serum glucose or systolic or diastolic blood pressure. Thus, ICAM-1 expression may share common genetic modulation with traits related to obesity, insulin resistance, and HDL3 cholesterol, but not with hyperglycemia or hypertension per se.
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PMID:Intercellular adhesion molecule-1 concentration is genetically correlated with insulin resistance, obesity, and HDL concentration in Mexican Americans. 1544 2

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11beta-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.
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PMID:Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers. 1564 56

The metabolic syndrome is a cluster of interrelated common clinical disorders, including obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol levels). According to recently defined criteria, the metabolic syndrome is prevalent and is associated with a greater risk of atherosclerotic cardiovascular disease than any of its individual components. Primary defects in energy balance that produce obesity (and visceral adiposity in particular) are sufficient to drive all aspects of the syndrome. Increased free fatty acids and lipid accumulation in certain organs are mediators of insulin resistance. Obesity also leads to a proinflammatory and prothrombotic state that potentiates atherosclerosis. Pathways leading directly from adiposity to the genesis of dyslipidemia and hypertension have been elucidated. Recent knowledge implies a role for fat-derived "adipokines," including TNF alpha and adiponectin, as pathogenic contributors or protective factors. Current therapies include diet and exercise as well as agents indicated for the treatment of individual components of the syndrome. Future therapies may accrue from the aggressive pursuit of newer molecular drug targets that have the potential to prevent or treat multiple aspects of the metabolic syndrome.
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PMID:Metabolic syndrome: a clinical and molecular perspective. 1566 May 1

Insulin resistance increases during the normal course of pregnancy, and is considered an important cause of complications including gestational diabetes mellitus, pregnancy-induced hypertension and preeclampsia (PE). Adiponectin, an adipocyte-specific plasma protein, is thought to enhance insulin sensitivity; another adipocytokine, leptin, also is thought to promote insulin sensitivity. We determined peripheral blood concentrations of adiponectin and leptin in 40 healthy nonpregnant women with a body mass index (BMI)<25, 40 healthy pregnant women with prepregnancy BMI<25, and 15 PE patients with prepregnancy BMI<25. Serum adiponectin concentrations were lower in the healthy pregnant group than in the nonpregnant group (9.40+/-4.43 versus 13.15+/-6.69 microg/mL, p<0.01), but difference disappeared after correction for haematocrit. Serum leptin concentrations were high in the normal pregnant group after correction for haematocrit (10.08+/-6.58 versus 6.24+/-3.61 ng/mL, p<0.05). Corrected after haematocrit, serum adiponectin in PE patients was higher than healthy pregnant women at 28 to 40 gestational weeks (17.46+/-11.81 versus 9.33+/-4.47 microg/mL, p<0.01). Leptin in PE was higher than in the normal pregnant group (21.15+/-19.89 versus 11.77+/-6.25 ng/mL, p<0.05), also after correction for haematocrit. These results suggested a metabolic shift in normal pregnant women and PE patients mediated through adipocytokines.
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PMID:Peripheral blood concentrations of adiponectin, an adipocyte-specific plasma protein, in normal pregnancy and preeclampsia. 1569 68

Adiponectin, an adipose-derived hormone, exhibits various biological functions, such as increasing insulin sensitivity, protecting hypertension, and suppression of atherosclerosis, liver fibrosis, and tumor growth. Here, we report the role of adiponectin on bone metabolism. C57BL/6J mice were treated with adenovirus expressing lacZ or adiponectin, and their bones were analyzed by three-dimensional microcomputed tomography. Adiponectin-adenovirus treatment increased trabecular bone mass, accompanied by decreased number of osteoclasts and levels of plasma NTx, a bone-resorption marker. In vitro studies showed that adiponectin inhibited M-CSF- and RANKL-induced differentiation of mouse bone marrow macrophages and human CD14-positive mononuclear cells into osteoclasts and also suppressed the bone-resorption activity of osteoclasts. Furthermore, adiponectin enhanced mRNA expression of alkaline phosphatase and mineralization activity of MC3T3-E1 osteoblasts. Our results indicate that adiponectin exerts an activity to increase bone mass by suppressing osteoclastogenesis and by activating osteoblastogenesis, suggesting that adiponectin manipulation could be therapeutically beneficial for patients with osteopenia.
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PMID:Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. 1585 Jul 90

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.
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PMID:Lifestyle modification and endothelial function in obese subjects. 1585 97

Recently, the genetic variability at adiponectin locus (APM1) was associated with cardiovascular risk in patients with type 2 diabetes. We sought to examine the associations of five variants of APM1 gene (C-11365G, A-4034C, A-3964G, T45G, and G276T) with the risk of cardiovascular diseases (CVDs) in a larger cohort of diabetic patients. Of 879 diabetic men from the Health Professionals Follow-up Study, 239 participants developed coronary heart disease or stroke during 14 years of follow-up and 640 CVD-negative subjects were used as control subjects. The risk of CVD was significantly lower in TT homozygotes at locus +276 than in other genotypes under a recessive inheritance model after adjusting for age, BMI, smoking, alcohol consumption, physical activity, aspirin use, HbA1c, and history of hypertension or hypercholesterolemia (odds ratio 0.38 [95% CI 0.18-0.79]; P = 0.009). In the CVD-negative control subjects, the allele 276T was associated with significantly higher plasma adiponectin levels in a dose-dependent pattern (GG 14.8, GT 16.2, and TT 18.8 microg/ml) after adjusting for age, BMI, and other variables (P for trend = 0.0019). In conclusion, our study showed significant associations between APM1 G276T and decreased CVD risk and increased plasma adiponectin levels in diabetic men.
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PMID:The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men. 1585 54

Being overweight or obese has become highly prevalent in Western countries and are rapidly reaching epidemic proportions in the developing world. Obesity-related disorders, such as hypertension and diabetes, are also increasing at an alarming rate. The relationship between obesity, hypertension and insulin resistance is well recognised, but the molecular mechanisms involved remain relatively poorly understood. Adipose tissue plays a key role in the pathogenesis of the metabolic syndrome. It serves as an important source of pro-inflammatory molecules, including leptin, tumour necrosis factor alpha, angiotensin II and interleukin-6, as well as anti-inflammatory molecules, such as adiponectin. Knowledge of how these adipose tissue-derived factors influence metabolic and cardiovascular disease has recently expanded. Leptin is now considered to play a key role in the elevation of sympathetic activity commonly found in obese, hypertensive patients, and decreased secretion of adiponectin appears to be an important predictor of diabetes. The ectopic storage of excess fat in skeletal muscle, liver or pancreas, due to the decreased capacity of adipose tissue to scavenge excess calories, may also play a role in the development of insulin resistance and type 2 diabetes. Overall, continuing research into the relationship between adipose-tissue biology and metabolic abnormalities may lead to a better understanding of the molecular mechanisms underlying the relationship between obesity and cardiovascular disease, and ultimately provide alternative treatments for the control of potentially life-threatening conditions.
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PMID:Obesity, hypertension and insulin resistance. 1586 17

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone (P<0.001 by ANOVA). When compared with simvastatin or ramipril alone, combined therapy significantly reduced high-sensitivity C-reactive protein levels (P=0.004 by ANOVA). Interestingly, combined therapy or ramipril alone significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.015 by ANOVA). Ramipril combined with simvastatin had beneficial vascular and metabolic effects when compared with monotherapy in patients with type 2 diabetes.
Hypertension 2005 Jun
PMID:Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. 1588 29

Obesity and its related disorders, glucose intolerance, hypertension and hyperlipidemia, collectively named the metabolic syndrome, result in substantial cardiovascular morbidity and mortality. Recent data point to several underlying regulatory mechanisms through which obesity links these various outcomes. Adipose tissue is now understood to function not merely as a passive energy storage depot but as an active endocrine organ, producing a variety of bioactive substances termed adipocytokines. Adiponectin, an adipocytokine first described as the most abundant protein produced by adipocytes, appears to serve as a central regulatory protein in many of the physiologic pathways controlling lipid and carbohydrate metabolism, and to mediate various vascular processes. Adiponectin displays both anti-inflammatory and antiatherogenic properties. Unlike other adipocytokines, its levels are paradoxically decreased in obesity and insulin-resistance states including metabolic syndrome and diabetes, as well as hypertension and coronary artery disease. This review will detail the relationship of adiponectin to various features of obesity and insulin-resistance syndromes, as well as its relationship to the cardiovascular complications of these disorders.
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PMID:Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. 1588 74


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