angiotensinogen and Metabolic-Syndrome

Elevated blood glucose, obesity, high blood pressure, elevated triglycerides and low high density lipoprotein (HDL) cholesterol are well accepted risk factors in the development of coronary artery disease. Clustering of at least three of these factors in an individual is defined as metabolic syndrome (MetS). Obesity is a central pathological mechanism in the disease and it is expected that the incidence of this condition will increase dramatically within the next years. The visceral adipose tissue is not only an energy depot but also an endocrine organ which produces a large number of bioactive molecules, the so called adipokines. In the setting of obesity, the over-production of proinflammatory and pro-thrombotic adipokines is associated with insulin resistance. This mechanism represents the pathophysiological basis for the development of MetS. Inflammation has a central role in the pathogenesis of MetS and in mediating its impact on the development of cardiovascular disease. Knowledge of these mechanisms has relevance in the context of preventive and therapeutic strategies.

Topics: Adiponectin; Adolescent; Adult; Angiotensinogen; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Endothelium, Vascular; Humans; Inflammation; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Life Style; Metabolic Syndrome; Obesity; Plaque, Atherosclerotic; Plasminogen Activator Inhibitor 1; Prognosis; Resistin; Risk; Tumor Necrosis Factor-alpha

Adipose tissue contains various types of cells that include preadipocytes and adipocytes. Studies have emphasized that (i) preadipocytes secrete factors involved in their own differentiation and (ii) adipocytes acquire the ability to communicate systemically with other organs (brain, liver, skeletal muscle) and locally with other cells (preadipocytes, endothelial cells and monocytes/macrophages). Adipocytes secrete proteins exhibiting either beneficial (leptin, adiponectin) or deleterious effects (angiotensinogen). Associated to the effect of secretory products from macrophages (cytokines), a disturbance in the balance between these various secreted factors leads to the development of a metabolic syndrome.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Angiotensinogen; Cell Communication; Humans; Leptin; Macrophages; Metabolic Syndrome

Topics: Adipose Tissue; Angiotensinogen; Animals; Animals, Genetically Modified; Humans; Metabolic Syndrome; Mice

Topics: Adipocytes; Adiponectin; Adipose Tissue; Angiotensinogen; Arteriosclerosis; Humans; Intercellular Signaling Peptides and Proteins; Life Style; Lipid Metabolism; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Risk Factors; Tumor Necrosis Factor-alpha; Viscera

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.

Topics: Adipocytes; Adipose Tissue, Brown; Angiotensin II; Angiotensinogen; Animals; Humans; Hypertension; Insulin Resistance; Metabolic Syndrome; Mice; Obesity; Peptidyl-Dipeptidase A; Rats; Renin; Renin-Angiotensin System; Thermogenesis

Metabolic syndrome (MetS) is associated with hypertension, obesity and dyslipidemia. Thus, genetic variants related with these conditions may modulate its development. We evaluated the effect of polymorphisms in the renin-angiotensin system (RAS) on metabolic syndrome risk in a cohort of Chilean subjects.. A total of 152 subjects, 83 with MetS (51.2 ± 9.6 years) and 69 without MetS (49.5 ± 9.3 years) of both genders were included, according to the ATP III update criteria. The rs4340 Insertion/Deletion (I/D), rs699 (T>C) and rs5186 (A>C) of the ACE, AGT and AGTR1 genes, respectively, were genotyped.. After adjusting for age and gender, we observed the DD genotype of rs4340 associated with MetS (p = 0.02). Specifically, the DD genotype was associated with MetS risk in women (OR = 4.62, 95%CI, 1.41 - 15.04; p < 0.01). In males, the AA genotype for rs5186 variant was associated with an increased risk for developing MetS when compared with women carrying the same genotype (OR = 3.2; 95%CI, 1.03 - 9.89; p = 0.04). In subjects without MetS, DD genotype was associated with increased waist circumference (p = 0.023) while subjects with MetS carrying the rs5186 TT genotype showed higher levels of HDL-cholesterol (p = 0.031).. The present study contributes data highlighting the role for RAS polymorphisms in predisposing to metabolic syndrome in Chilean subjects.

Topics: Adult; Age Factors; Aged; Angiotensinogen; Chile; Cohort Studies; Cross-Sectional Studies; Female; Gene Deletion; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Sex Factors

Changes in the frequencies of genotypes and mutant alleles of ACE, AGTR1, AGT, and ITGB3 genes were analyzed in patients with arterial hypertension coupled with metabolic syndrome (N=15) and compared with population data and corresponding parameters in patients with isolated hypertension (N=15). Increased frequency of genotype ID of ACE gene (hypertension predictor) was confirmed for both groups. In case of isolated hypertension, M235M genotype (gene AGT) was more frequent, in case of hypertension combined with metabolic syndrome, the frequency of genotypes A1166C and C1166C of the gene AGTR1 was higher in comparison with population data. Comparison of mutant allele frequencies in the two groups showed that at the 90% significance level allele T of the AGT gene was more frequent in hypertension coupled with metabolic syndrome (OR=1.26) and genotype A1166A of the AGTR1 gene was more frequent in the group with isolated hypertension.

Topics: Aged; Angiotensinogen; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Integrin beta3; Male; Metabolic Syndrome; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated.. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model.. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined.. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression.. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension.

Topics: Angiotensinogen; Animals; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Dihydrotestosterone; Disease Models, Animal; Estradiol; Female; Glomerular Filtration Rate; Glucose Tolerance Test; Kidney Diseases; Leptin; Metabolic Syndrome; Oxidative Stress; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System

The genes associated with hypertension could be genetic risk factors for metabolic syndrome (MetS).. To determine the frequency of M235T and T174M-AGT, I/D-ACE and A1166C-AGTR1 in hypertensive patients with MetS and to evaluate the relationship between these polymorphisms and central obesity and dyslipidemia, respectively.. We performed AGT, AGTR1 and ACE genotyping in 56 hypertensive women (24 with MetS) and 71 normotensive women using PCR-RFLP methods and PCR, respectively.. Hypertensive patients carrying the mutated TT235, MM174 and DD genotypes had an 1.53 (p=0.56), 1.78 (p=0.52) and 1.28 (p=0.78)-fold increased risk to develop MetS. Hypertensive carriers of both mutated TT235 and MM174 or TT235 and D/D or TT235 and CC+AC genotypes had an 8.15 (p=0.04), 4.83 (p=0.04) and 10.53 (p=0.05)-fold increased risk to develop MetS. Hypertensive patients with MetS and TT, D/D or CC genotypes had higher body mass index compared to hypertensive patients without MetS (p

Topics: Adult; Angiotensinogen; Dyslipidemias; Female; Genetic Predisposition to Disease; Genotype; Humans; Hypertension, Renal; Metabolic Syndrome; Middle Aged; Obesity; Peptidyl-Dipeptidase A; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Factors

To investigate the renin-angiotensin system (RAS) in mesenteric adipose tissues and effect of angiotensin II on adipocyte differentiation.. Thirty normal 8-week-old male Wistar rats were divided into groups on normal diet and high-fat diet. The rats on high-fat diet for 24 weeks developed the metabolic syndrome respectively. The mRNA and protein expression of mesenteric adipose tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Lipid drop in 3T3-L1 preadipocytes and mature adipocytes were observed using oil-red O staining. The fluorescence microscope was used to detect cytosolic-free calcium in 3T3-L1 preadipocytes and mature adipocytes.. The expressions of angiotensinogen, angiotensin converting enzyme, angiotensin II receptor type 1 in mesenteric adipose tissue were significantly increased in rats with metabolic syndrome compared with those in rats on normal diet (P <0. 05, P <0. 01). After administration of angiotensin II , no lipid droplet in 3T3 -L1 preadipocytes and adipocytes were observed, however, intensive lipid droplet in adipocyte was found after administration of captopril and candesartan. Angiotensin II increased the intracellular-free calcium concentration in preadipocytes (P < 0. 01 ) , which was blocked by captopril and candesartan; in contrast, angiotensin II effect was blunt in mature adipocyte. Captopril and candesartan partially recovered the angiotensin II -mediated increase of cytosolic-free calcium.. RAS in the mesenteric adipose tissues is active in rats with metabolic syndrome, and antagonization of RAS can recover the lipogenesis of adipocyte.

Topics: Adipocytes; Adipose Tissue; Angiotensin II; Angiotensinogen; Animals; Benzimidazoles; Biphenyl Compounds; Calcium; Captopril; Cells, Cultured; Male; Metabolic Syndrome; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tetrazoles