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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is an important risk factor for heart disease. Whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. We hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. We examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese KKAy mice. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) into KKAy mice fed ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). The 14-day survival rate was 0% in FF, whereas it was 23% in RF (P<0.01). Heart weight/body weight ratio in RF was lower than that in FF on day 5 after viral inoculation (P<0.05). Histological scores for myocardial necrosis and inflammation on day 5 were significantly lower in RF than in FF (P<0.05). Circulating adiponectin level on day 0 was significantly elevated in RF compared with that in FF (32+9 vs. 22+2 microg/mL, P<0.05). Comparative expression of cardiac adiponectin mRNA in RF was significantly higher than that in FF (5.1+0.3 vs. 1+0.2, P<0.05). Cardiac tumor necrosis factor-alpha (TNF-alpha) mRNA in RF was significantly decreased compared with that in FF on day 5 (P<0.05). Cardiac expression of nuclear factor kappa B was reduced and that of peroxisome proliferator-activated receptor gamma mRNA was increased in RF in comparison with FF on day 0. Cardiac adiponectin mRNA was negatively correlated with cardiac TNF-alpha mRNA (r=-0.555; P=0.0097). Weight loss improved the survival and myocardial damage in obese mice with viral myocarditis, with cardiac induction of adiponectin. The induction of adiponectin might provide benefit through a cardioprotective effect against acute heart failure due to viral myocarditis in obese subjects.
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PMID:Reduced-energy diet improves survival of obese KKAy mice with viral myocarditis: induction of cardiac adiponectin expression. 1727 7

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, cardiogenic shock, and sudden cardiac death in women of reproductive age who have no traditional risk factors for coronary artery disease. The etiology, prognosis, and treatment of SCAD remain poorly defined. Coronary angiography is the gold standard for diagnosis. Management includes medical therapy and revascularization procedures using percutaneous intervention and coronary artery bypass grafting. Possible mechanisms of SCAD include rupture of atherosclerotic plaque or vasa vasorum, hemorrhage between the outer media and external lamina with intramedial hematoma expansion, and compression of the vessel lumen. We report a case of SCAD in a 39-year-old woman presenting with ST-elevation myocardial infarction midway through her menstrual cycle. Her medications included fenfluramine for obesity and hydrochlorothiazide, amlodipine, and atenolol for hypertension.
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PMID:Spontaneous coronary artery dissection in a woman on fenfluramine. 1740 2

Metabolic syndrome has the unique concept that the common occurrence of individual disease components increases the risk of coronary artery disease (CAD). However, some studies suggest that the burden of different CAD risk factors is not equal, and focusing on the whole set of risk factors might neglect the impact of individual factors that could be useful targets for prophylactic therapies. The purpose of this study was to investigate the effect of glucose intolerance on CAD using multislice computed tomography (MSCT). Ninety-eight consecutive patients with at least one traditional CAD risk factor who visited a municipal hospital were enrolled in this study. The risk factors were impaired glucose tolerance (fasting glucose > or = 110 mg/dl or patients with diabetes), low high-density lipoprotein cholesterol (HDL-C, < 40 mg/dl for men and < or = 50 mg/dl for women), hypertriglycemia (triglyceride > or = 150 mg/dl), hypertension (blood pressure > or = 130/85 mmHg), and obesity (body mass index, > 25 kg/m(2) for men and > 23 kg/m(2) for women). CAD was determined by the presence of either stenoses, non-calcified plaques or calcified lesions. The following risk factors were significantly related in univariate logistic models: glucose intolerance and coronary calcified lesions (p = 0.001), and hypertriglycemia and non-calcified plaque lesions (p = 0.048). Multivariate models showed that glucose intolerance was significantly associated with calcified lesions, even after adjustment for gender, age, low HDL-C, hypertriglycemia, hypertension, and obesity (p = 0.018). Our results suggest that glucose intolerance might be closely related to the presence of coronary calcified lesions among traditional CAD risk factors.
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PMID:Impact of glucose intolerance on coronary calcified lesions evaluated using multislice computed tomography. 1754 55

Macrophages orchestrate an inflammatory response that contributes to glucose intolerance in diet-induced obesity and plaque instability in atherosclerosis. Within this heterogeneous group of cells are proinflammatory (M1) and anti-inflammatory (M2) macrophages. Recent work has identified the nuclear hormone receptor PPARgamma as a critical signaling molecule in determining macrophage phenotype in vitro and in adipose tissue. In the current issue of Cell Metabolism, Bouhlel et al. (2007) extend this paradigm to the vessel wall by showing that both M1 and M2 macrophages are present in atherosclerotic lesions and that activation of PPARgamma polarizes circulating blood monocytes to become M2 macrophages.
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PMID:Macrophage polarization and insulin resistance: PPARgamma in control. 1768 Nov 49

Chronic plaque psoriasis is an immune-mediated, inflammatory skin disease with a heavy burden on quality of life of patients. The disease has a chronic relapsing course and may be life long. Comorbid disorders include psoriatic arthritis, obesity, dyslipidemia, hypertension and an increased rate of cardiovascular disease. Conventional systemic treatments include methotrexate, cyclosporine and acitretin, which are associated with end organ toxicity that precludes long term therapy. Biological drugs are designed to selectively interfere with the immune mechanisms that induce psoriasis. Efalizumab is effective for skin psoriasis but not psoriatic arthritis. Anti-TNF-alpha agents (etanercept, infliximab and adalimumab) are active on both psoriasis and psoriatic arthritis. Infliximab is the most effective and rapid agent, but its safety profile may be less favourable. Moreover, efficacy can reduce over time. Etanercept is moderately active but has a better safety profile, and can be discontinued and re-used without loss of efficacy. The long term safety of all these agents has not been established.
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PMID:Biologic therapies in psoriasis: a new therapeutic approach. 1785 41

Epidemiologic data indicate a large increase in cardiovascular risk in patients with systemic lupus erythematosus (SLE). Non-invasive investigations show increases in intima-media thickness, carotid plaque, and coronary artery calcifications in patients with SLE, compared to controls. Conventional cardiovascular risk factors may fail to fully explain the high cardiovascular risk in SLE patients. Immunological disturbances and inflammation may indirectly contribute to the risk of cardiovascular disease by inducing dyslipidemia and/or insulin resistance. The potential role for glucocorticoid therapy is controversial. Effective control of the disease would be expected to decrease the cardiovascular morbidity and mortality rates. Careful attention should be given to controlling conventional risk factors such as obesity, smoking, and physical inactivity. Hypertension and/or dyslipidemia should be treated optimally. The appropriateness of antiplatelet therapy should be assessed.
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PMID:Atheroma and systemic lupus erythematosus. 1786 65

We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia and chronic hyperglycemia play a role in the atherosclerotic process and may require intervention 67. Moreover, it is important to recognize that these risk factors frequently "cluster" inindividual patients and possibly interact with each other, favouring the atherosclerosis progression toward plaque instability. Thus, a fundamental question is, "which is the common soil hypothesis that may unifying the burden of all these factors on atherosclerosis of diabetic patients? Because evidences suggest that insulin-resistance, diabetes and CHD share in common a deregulation of ubiquitin-proteasome system (UPS), the major pathway for nonlysosomal intracellular protein degradation in eucaryotic cells 89, in this review ubiquitin-proteasome deregulation is proposed as the common persistent pathogenic factor mediating the initial stage of the atherosclerosis as well as the progression to complicated plaque in diabetic patients.
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PMID:The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes. 1797 Dec 5

Recent epidemiologic, pathologic, and intravascular ultrasound (IVUS) studies have shown that there are differences in coronary risk factors or plaque morphology between younger and older patients with acute myocardial infarctions (AMIs). This study examined clinical background and plaque morphology using IVUS in younger and older adults with AMIs in Japan. The study population consisted of 96 patients with AMIs, for whom preinterventional IVUS images were obtained. Patients were classified into 3 groups: a young group (aged < or =55 years), a middle-aged group (aged 56 to 69 years), and an old group (aged > or =70 years). The remodeling index was defined as the ratio of the external elastic membrane area at the culprit lesion to the external elastic membrane area at the proximal reference site. Expansive remodeling was defined as a remodeling index >1.05 and constrictive remodeling as a remodeling index <0.95. The frequency of hypercholesterolemia was significantly different among the 3 age groups. Total cholesterol (p <0.001), low-density lipoprotein cholesterol (p <0.005), and triglyceride (p <0.05) levels and body mass index (p <0.001) in the young group were significantly higher than in the old group. On IVUS images, constrictive remodeling was most common in the young group, whereas expansive remodeling occurred most commonly in the middle-aged and old groups. In conclusion, this study demonstrated that patients with AMIs in the young group had higher levels of hypercholesterolemia, obesity, and constrictive remodeling compared with those in the old group. The differences in arterial remodeling of the culprit lesions between younger and older patients with AMIs may reflect different biologic mechanisms of plaque activation and destabilization.
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PMID:Comparison of clinical characteristics and arterial remodeling by intravascular ultrasonic imaging in three age groups (< or =55, 56 to 69 and > or =70 years) of Japanese patients with acute myocardial infarction. 1847 76

The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E (Apoe(-/-)) or low-density lipoprotein receptor (Ldlr(-/-)) and express no leptin (Lep(ob/ob)) or apolipoprotein B-48 but exclusively apolipoprotein B-100 (Apob(100/100)). These two lines are referred to as Apoe triple-knockout-Apoe 3KO (Apoe(-/-)Apob(100/100)Lep(ob/ob)) and Ldlr triple-knockout-Ldlr 3KO (Ldlr(-/-)Apob(100/100)Lep(ob/ob)) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therapy ameliorated most metabolic derangements. Leptin was more effective in improving glucose tolerance in Ldlr 3KO than Apoe 3KO animals. The reduction of plasma cholesterol by leptin in Ldlr 3KO mice can be accounted for by its suppressive effect on food intake. However, in Apoe 3KO mice, leptin further reduced plasma cholesterol independently of its effect on food intake, and this improvement correlated with a smaller plaque lesion area. These effects suggest a direct role of leptin in modulating VLDL levels and, likewise, the lesion areas in VLDL-enriched animals. These two lines of mice represent new models with features of the metabolic syndrome and will be useful in testing therapies targeted for combating the human condition.
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PMID:Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome: Apob48-/-Lepob/ob mice devoid of ApoE or Ldlr. 1816 Apr 59

Type 2 diabetes mellitus, a global epidemic, is largely attributed to metabolic syndrome and its clustering of cardiovascular risk factors including abdominal obesity, dyslipidemia, hypertension and hyperglycemia. The two primary approaches to optimally control risk factors associated with metabolic syndrome are lifestyle changes and medications. Although many pharmacological targets have been identified, clinical management of cardiovascular risk factors associated with metabolic syndrome and type 2 diabetes is still dismal. Recent evidence suggests premises of the peroxisome proliferator-activated receptor (PPAR) ligands in the combat against type 2 diabetes and metabolic syndrome including obesity and insulin resistance. Three subtypes of the PPAR nuclear fatty acid receptors have been identified: alpha, beta/delta and gamma. PPARalpha is believed to participate in fatty acid uptake (beta- and omega-oxidation) mainly in the liver and heart. PPARbeta/delta is involved in fatty acid oxidation in muscle. PPARgamma is highly expressed in fat to facilitate glucose and lipid uptake, stimulate glucose oxidation, decrease free fatty acid level and ameliorate insulin resistance. Synthetic ligands for PPARalpha and gamma such as fibric acid and thiazolidinediones have been used in patients with type 2 diabetes and pre-diabetic insulin resistance with significantly improved HbA(1c) and glucose levels. In addition, nonhypoglycemic effects may be elicited by PPAR agonists or dual agonists including improved lipid metabolism, blood pressure control and endothelial function, as well as suppressed atherosclerotic plaque formation and coagulation. However, issues of safety and clinical indication remain undetermined for use of PPAR agonists for the incidence of heart disease in metabolic syndrome and type 2 diabetes.
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PMID:Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus. 1822 Jun 54


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