endothelin-1 and Weight-Loss

Pulmonary hypertension (PH) is a frequent complication of left heart disease arising from a wide range of cardiac disorders. In the clinical classification, PH associated with left heart disease is classified as Group 2, which includes left heart systolic dysfunction, left heart diastolic dysfunction and left heart valvular disease. In the past, rheumatic mitral valve disease was the most common cause of PH in left heart disease; however, today it is more likely to be associated with hypertensive and/or ischaemic heart disease. As the incidence of these conditions is increasing, the number of patients presenting with PH is also increasing and, today, left heart disease represents the most frequent cause of PH. The development of PH in patients with left heart disease is associated with poor prognosis. However, despite the increasingly large number of patients affected and the impact of PH on outcome, there are currently no specific treatment options for these patients. This review gives an overview of the pathophysiology and epidemiology of PH associated with left heart disease, and discusses the challenges associated with its management and treatment.

Topics: Antihypertensive Agents; Bosentan; Echocardiography, Doppler; Electrocardiography; Endothelin A Receptor Antagonists; Endothelin-1; Endothelium, Vascular; Exercise Test; Heart Valve Prosthesis; Humans; Hypertension, Pulmonary; Mitral Valve; Nitric Oxide; Phosphodiesterase 5 Inhibitors; Pulmonary Wedge Pressure; Radiography, Thoracic; Stroke Volume; Sulfonamides; Vascular Resistance; Vasodilator Agents; Ventricular Dysfunction, Left; Weight Loss

Topics: Biomarkers; Body Mass Index; Cachexia; Chronic Disease; Echocardiography; Endothelin-1; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Time Factors; Troponin I; Weight Loss

Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 ± 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 ± 0.6 kg vs. -3.6 ± 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Diet Records; Diet, Reducing; Endothelin-1; Endothelium, Vascular; Exercise; Humans; Japan; Life Style; Male; Middle Aged; Nitric Oxide; Obesity; Overweight; Oxygen Consumption; Risk Factors; Vascular Stiffness; Waist Circumference; Walking; Weight Loss

Endothelial dysfunction and inflammation are present in both type 2 diabetes mellitus (T2DM) and obesity. In this paper we compared the role of weight loss and of glycaemic control in determining circulating levels of ICAM-1, endothelin-1 (ET-1), and E-selectin in patients with morbid (grade 3) obesity.. ICAM-1, E-selectin, and ET-1 were higher in obese patients (n=96) than in lean controls (n=30); among obese patients, the three molecules were higher in T2DM patients (n=26) than in patients with normal (NGT, n=43) or impaired (IGT, n=27) glucose tolerance. Sixty-eight obese patients had a significant weight loss induced by bariatric surgery, and showed a significant decrease in blood glucose, HbA1c and all molecules, so that ICAM-1, E-selectin, and ET-1 were not different in NGT, IGT and T2DM patients, and in lean controls; in 13 patients with a small weight loss induced by diet, changes were not significant, in spite of a significant reduction in blood glucose and HbA1c. At stepwise regression, changes in ICAM-1, ET-1, and E-selectin significantly correlated only with change in body mass index.. These data indicate that weight loss is more important than glycaemic control in regulating circulating levels of ICAM-1, ET-1, E-selectin in morbidly obese subjects.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; E-Selectin; Endothelin-1; Female; Follow-Up Studies; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin Resistance; Intercellular Adhesion Molecule-1; Male; Matched-Pair Analysis; Middle Aged; Obesity, Morbid; Reference Values; Regression Analysis; Weight Loss

Previous evidence has implied that obesity is an independent risk factor for developing cancer. Being closely related to obesity, type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways. Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer, the underlying mechanisms of this effect are not clearly elucidated.. To uncover the role and effect of sleeve gastrectomy (SG) in preventing lung cancer in obese and diabetic rats.. SG was performed on obese and diabetic Wistar rats, and the postoperative transcriptional and translational alterations of the endothelin-1 (ET-1) axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4. Compared to obese and diabetic sham-operated rats, SG brought a significant reduction to body weight, food intake, and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity. In addition, ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery.. Apart from eliminating metabolic disorders, SG improves endothelial function and plays a protective role in preventing lung cancer

Topics: Animals; Bariatric Surgery; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; DNA Breaks, Double-Stranded; Endothelin-1; Endothelium; Glucose Tolerance Test; Histones; Humans; Lung; Lung Neoplasms; Male; Obesity; Phosphoproteins; Phosphorylation; Rats; Streptozocin; Weight Loss

Obesity and insulin resistance are positively correlated with plasma endothelin-1 (ET-1) levels; however, the mechanisms leading to increased ET-1 are not understood. Similarly, the full physiological complexity of ET-1 has yet to be described, especially in obesity. To date, one of the best treatments available for morbid obesity is bariatric surgery to quickly reduce body fat and the factors associated with obesity-related disease; however, the effects of vertical sleeve gastrectomy (SG) on plasma ET-1 have not been described.. To determine if SG will reduce plasma ET-1 levels and to determine if plasma ET-1 concentration is associated with weight loss after surgery.. The studies were undertaken at a University Hospital.. This was tested by measuring plasma ET-1 levels from 12 obese patients before and after SG. All data were collected from clinic visits before SG, 6 weeks after SG, and 6 months after surgery.. At 6 weeks after SG, plasma ET-1 levels increased by 24%; however, after 6 months, there was a 27% decrease compared with presurgery. Average weight loss in this cohort was 11.3% ± 2.4% body weight after 6 weeks and 21.4% ± 5.7% body weight after 6 months. Interestingly, we observed an inverse relationship between baseline plasma ET-1 and percent body weight loss (R. Our results indicate that SG reduces plasma ET-1 levels, a possible mechanism for improved metabolic risk in these patients. These data also suggest that ET-1 may serve as a predictor of weight loss after bariatric surgery.

Topics: Adult; Bariatric Surgery; Body Mass Index; Cohort Studies; Endothelin-1; Female; Gastrectomy; Humans; Male; Middle Aged; Obesity, Morbid; Time Factors; Treatment Outcome; Weight Loss

The aim of this study was to determine if weight loss following Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of the renin angiotensin system (RAS), catecholamines and endothelin-1, and also with an increase in the concentrations of vasodilators. Fasting blood samples were obtained from 15 patients with morbid obesity and diabetes prior to and 6 months after RYGB surgery. Circulating levels of neprilysin, vasoconstrictors, vasodilators, and the mRNA expression of related genes in circulating mononuclear cells (MNC) were measured. Six months after RYGB surgery the concentrations of neprilysin, angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27 ±16%, 22 ±10%, 22 ±8%, 35 ±13% and 17 ±6% (P < .05 for all), respectively, while ANP concentrations increased significantly by 24 ±13%. There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations, or angiotensin converting enzyme (ACE) expression. These changes may contribute to the reduction of congestive cardiac failure and blood pressure risks after RYGB surgery.

Topics: Bariatric Surgery; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Endothelin-1; Female; Glycated Hemoglobin; Heart Failure; Humans; Hypertension; Insulin Resistance; Male; Middle Aged; Neprilysin; Obesity, Morbid; Postoperative Period; Prospective Studies; Renin-Angiotensin System; Risk; Weight Loss

Weight loss improves endothelial function in overweight individuals. The effects of weight loss through combined aerobic and resistance training and caloric restriction on in vivo vascular measures and blood markers associated with the regulation of endothelial function have not been comprehensively examined. Therefore, we investigated brachial artery endothelial function and potential regulatory blood markers in twenty overweight women (30.3 ± 2.0 years) who participated in 16 weeks of aerobic (5 d/wk) and resistance training (2 d/wk) (combined: ≥ 250 kcal/d) and caloric restriction (-500 kcal/d versus requirement). Resting brachial artery flow mediated dilation (FMD) and circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) were assessed at baseline and following the intervention. Relative and absolute FMD increased (before: 4.0 ± 0.5% versus after: 6.9 ± 0.6%, P < 0.05, and before: 0.14 ± 0.02 mm versus after: 0.23 ± 0.02 mm, P < 0.05, resp.), while body mass decreased (before: 86.9 ± 2.4 kg versus after: 81.1 ± 2.4 kg, P < 0.05) following the intervention. There were no changes in either blood marker (IL-6: before: 1.5 ± 0.2 pg/mL versus after: 1.5 ± 0.1 pg/mL, P > 0.05, and ET-1: before: 0.55 ± 0.05 pg/mL versus after: 0.59 ± 0.09 pg/mL, P > 0.05). 16 weeks of combined aerobic/resistance training and diet-induced weight loss improved endothelial function in overweight and obese young women, but this increase was not associated with changes in blood markers of vasoconstriction or inflammation.

Topics: Adult; Body Composition; Diet; Endothelin-1; Endothelium, Vascular; Energy Intake; Exercise Therapy; Female; Humans; Obesity; Overweight; Resistance Training; Weight Loss

Decrease of both visceral fat (surgery, physical exercise) and subcutaneous fat (liposuction) is accompanied by improvement of insulin sensitivity.. In this study, metabolic variables (glucose, insulin, high-density lipoprotein-cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, uric acid, ferritin) and adhesion molecules (ICAM-1, entothelin-1, E-selectin) were determined in 126 morbidly obese subjects before and 1 year after bariatric restrictive surgery (laparoscopic gastric banding) and correlated with anthropometric measures, i.e., body mass index (BMI) and waist circumference (waist), and with echographic measures of thickness of visceral (usVT) and subcutaneous (usST) abdominal fat.. Under basal conditions and after 1 year, metabolic variables correlated with BMI and waist (r from 0.157 to 0.507, p from 0.0182 to 0.0001) and with usVT (r from 0.211 to 0.512, p from 0.05 to 0.0001); insulin also correlated with usST, and adhesion molecules only correlated with BMI and usVT (r from 0.341 to 0.502, p from 0.0066 to 0.0001). Changes of metabolic variables correlated with changes of BMI and waist (r from 0.163 to 0.356, p from 0.0328 to 0.0001) and with usVT changes (r from 0.211 to 0.361, p from 0.0339 to 0.0002); changes of adhesion molecules only correlated with BMI and usVT changes (r from 0.227 to 0.361, p from 0.0444 to 0.0108). Changes of metabolic variables and of adhesion molecules virtually never correlated with changes of usST.. These data indicate that in morbid obesity, most metabolic abnormalities are associated with visceral fat and that their improvements after weight loss are associated with decrease of visceral fat.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Fat Distribution; Body Mass Index; Body Weight; E-Selectin; Endothelin-1; Female; Gastroplasty; Humans; Insulin; Intercellular Adhesion Molecule-1; Intra-Abdominal Fat; Male; Middle Aged; Obesity, Morbid; Regression Analysis; Subcutaneous Fat, Abdominal; Ultrasonography; Weight Loss; Young Adult

Obesity is associated with endothelial dysfunction that may contribute to the development of diabetes, hypertension, and atherosclerosis. Endothelin-1 (ET-1), which is produced mostly by vascular endothelial cells, has potent vasoconstrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and the progression of atherosclerosis, suggesting that ET-1 may be important in endothelial dysfunction. We studied whether diet-induced weight loss (i.e., lifestyle modification) affects plasma ET-1 concentration in obese individuals. We measured plasma ET-1 concentration in seven obese men (age: 48 +/- 4 years old, body mass index: 27.7 +/- 0.5 kg/m2) before and after a 3-month, diet-induced weight reduction program (i.e., lifestyle modification program). Caloric restriction reduced body weight from 78 +/- 3 to 68 +/- 2 kg (P < 0.001) and resulted in 12.1 +/- 1.2% reduction in body mass index (24.3 +/- 0.3 kg/m(2), P < 0.0001). After the weight reduction program, systolic and diastolic blood pressure significantly decreased (128 +/- 7 vs. 115 +/- 4 mm Hg, P < 0.05 and 88 +/- 4 vs. 77 +/- 2 mm Hg, P < 0.01, respectively). The plasma level of ET-1 significantly decreased after the program (5.1 +/- 0.4 vs. 4.0 +/- 0.3 pg/ml, P < 0.05). The percentage systolic blood pressure reduction and percentage plasma ET-1 concentration reduction was in a linear relationship (r = 0.86, P < 0.05). Furthermore, the relationship between percentage weight reduction and percentage plasma ET-1 concentration reduction was linear (r = 0.87, P < 0.05). We conclude that weight loss by low-calorie diet (i.e., lifestyle modification) reduces plasma ET-1 concentration in obese individuals. This reduction may contribute to the improvement of obesity-induced endothelial dysfunction.

Topics: Adult; Blood Pressure; Body Mass Index; Body Weight; Endothelin-1; Humans; Life Style; Male; Middle Aged; Obesity; Weight Loss