Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine patients with metastatic carcinoma involving the liver were treated by hepatic arterial chemotherapy with Angiotensin II (AGT II) using a subcutaneous implanted pump. There were two primary lesions in the breast, one in the stomach, three in the colon and three in the rectum. Every patient received intra-arterial bolus injection of 5-FU and Adriamycin with 3 mcg of AGT II weekly at our outclinic. Of 7 evaluable patients, 6 responded clinically with PR (response rate, 85.7%). No adverse effects were noted in relation to AGT II. AGT II combined with chemotherapy is therefore a safe and effective method for even outpatients with liver metastases.
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PMID:[Intra-arterial chemotherapy with angiotensin II in metastatic carcinoma of the liver using implantable pump]. 278 2

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.
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PMID:Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. 1049 84

Recent studies have shown that F2-isoprostane levels-a marker for lipid peroxidation-are increased in human renovascular hypertension but not in essential hypertension. Angiotensin II specifically stimulates F2-isoprostane production through activation of the AT1 receptor. The objective was to determine whether there is a relationship between the level of oxidative stress evaluated by measuring urinary F2-isoprostanes levels and polymorphisms of genes involved in the renine angiotensin aldosterone system (RAAS) regulation. The population studied included 100 subjects, 65 of whom were healthy normotensives; the other 35 were suffering from untreated, essential hypertension. The polymorphisms studied concern the genes encoding angiotensin I-converting enzyme (ACE/in16del/ins), angiotensin II receptor type I (AGTR1/A+39C[A+1166C] and AGTR1/A-153G), angiotensinogen (AGT/M235T), and aldosterone synthase (CYP11B2/T344C). Oxidative stress was evaluated by measuring urinary F2-isoprostanes levels. The characteristics of the population were as follows: men/women = 46/56; age = 50 +/- 10 years; BMI = 24 +/- 3 kg/m2; SBP = 131.7 +/- 17.2 mm Hg; DBP = 84.6 +/- 10.4 mm Hg. In univariate analysis, urinary F2-isoprostane levels were significantly lower in the presence of the G allele of AGTR1/A-153G (56 +/- 17 vs 76 +/- 39 pmol/mmol creatinine; P < 0.001, and P < 0.01 after Bonferroni correction for 10 tests). In multivariate analysis, taking into account BP, age, gender, BMI, plasma glucose, and total cholesterol, the G allele of AGTR1/A-153G is linked independently to urinary F2-isoprostanes level (P < 0.01). Our data suggest that F2-isoprostane level depends at least in part on the A-153G polymorphism of the angiotensin II AT1 receptor gene. The clinical and prognostic relevance of this polymorphism requires further investigation.
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PMID:F2-Isoprostane level is associated with the angiotensin II type 1 receptor -153A/G gene polymorphism. 1568 14

The aim of our study was to evaluate whether any association exists between metabolic syndrome (MS) and ACE I/D and AGT M235T gene polymorphisms in Hungarians as an example of European Caucasian population. Study subjects of our cross-sectional study were recruited from the Hungarian General Practitioners' Morbidity Sentinel Stations Program. The study population (n = 1762) approximates very well the age and sex distribution of the general Hungarian population. MS was defined according to the latest diagnostic criteria proposed by the International Diabetes Federation. The frequency of DD genotype (31.36% vs. 25.42%, p = 0.006) and the frequency of D allele (0.56 vs. 0.51, p = 0.006) were significantly higher in the metabolic group than in the non-metabolic group. The distribution of the AGT M235T polymorphism was similar in each group investigated. Association was shown in the case of patients in whom central obesity was combined with elevated TG and low HDL cholesterol level (p = 0.024 and p = 0.022). It suggests that ACE I/D polymorphism is likely to be involved in lipid metabolism.
J Renin Angiotensin Aldosterone Syst 2011 Dec
PMID:Insertion/deletion polymorphism of angiotensin-1 converting enzyme is associated with metabolic syndrome in Hungarian adults. 2133 Apr 20

The genes of the renin--angiotensin system (RAS) play an important role in the regulation of pulmonary vascular tone. Although studies on individual genes polymorphisms have reported association with high-altitude pulmonary oedema (HAPE), studies on multiple genes or epistasis are lacking. We therefore investigated the association of the RAS polymorphisms with HAPE. In a case-control design, we screened 163 HAPE-resistant/controls (HAPE-r) and 160 HAPEpatients (HAPE-p) of Indian origin for eight polymorphisms of four RAS genes, ACE, AGT, AGTR1 and AGTR2. Significant difference in genotype and allele frequencies of the ACE I/D and AGT M235T polymorphisms was observed between HAPE-p and HAPE-r (p < 0.05). In three-locus haplotype analysis of AGT the haplotype GTM was significantly higher in HAPE-p (29%) and haplotype GTT in HAPE-r (27%) after Bonferroni correction (p < 0.006). The differences were insignificant for polymorphisms from AGTR1 and AGTR2. The MDR (multifactor dimensional reduction) approach for gene--gene interaction depicted individual polymorphism M235T as the best disease predicting model (cross validation consistency, CVC = 10/10). We found a significant association of D allele of ACE and M allele of AGT with HAPE. The findings are supported at the haplotypic level as well as through nested genetic interaction between the RAS gene polymorphisms using the MDR approach.
J Renin Angiotensin Aldosterone Syst 2011 Jun
PMID:Polymorphisms of renin--angiotensin system genes as a risk factor for high-altitude pulmonary oedema. 2139 62

Angiotensin II (AGT-2) induces follicular prostaglandin release in a number of species and ovulation in rabbits. Conversely, AGT-2 antagonists block ovulation in cattle. To determine the mechanism of action of AGT-2, we used a bovine granulosa cell model in which luteinizing hormone (LH) increased the expression of genes essential for ovulation in a time- and dose-dependent manner. The addition of AGT-2 to LH-stimulated cells significantly increased abundance of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA and protein, whereas AGT-2 alone had no effect. Upstream of PTGS2, AGT-2 increased abundance of mRNA encoding the epidermal growth factor-like ligands amphiregulin (AREG) and epiregulin (EREG) at 6 h posttreatment and abundance of a disintegrin and metalloprotease 17 (ADAM17), a sheddase, within 3 h of treatment. Inhibiting sheddase activity abolished the stimulatory effect of AGT-2 on AREG, EREG, and PTGS2 mRNA. The addition of selective AGT-2 antagonists to cells stimulated with LH plus AGT-2 demonstrated that AGT-2 did not act through the type 1 receptor and did not increase mitogen-activated protein kinase 3/1 phosphorylation. Combined with previous data from studies in vitro, we conclude that AGT-2 is an essential cofactor for LH in the early increase of ADAM expression/activity that induces the cascade of events leading to ovulation.
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PMID:Role of angiotensin II in the periovulatory epidermal growth factor-like cascade in bovine granulosa cells in vitro. 2184 8

Chronic kidney disease (CKD) is highly prevalent in Taiwan and an increasing number of patients are affected, with a high risk of progression to end-stage renal disease and huge medical expenses. It has been predicted that the presence of hypertension increases with decreasing renal function due to a decrease in sodium excretion and activation of the renin-angiotensin system (RAS). The aim of this study was to investigate the influence of genetic variants of the RAS gene on CKD. We performed a case control association study and genotyped 135 CKD patients and 270 healthy controls among Han Chinese in Taiwan. All subjects were genotyped for angiotensinogen (AGT-M235T, T174M, A-20C), angiotensin-I converting enzyme (ACE-A2350G) and angiotensin II type 1 receptor (AGTR1-A1166C, C573T, C-521T) polymorphisms of RAS genes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Significant associations were observed in ACE-A2350G and AGTR1-C573T polymorphism between CKD patients and controls. In regard to ACE-A2350G, compared with the AA genotype the GG genotype protected against CKD (adjusted odds ratio [OR] = 0.34; p = 0.01). In regard to AGTR1-C573T, the CT genotype was a risk for CKD compared with the CC genotype (adjusted OR = 1.82; p = 0.03). We conclude that ACE-A2350G and AGTR1-C573T polymorphisms are likely candidate determinants of CKD.
J Renin Angiotensin Aldosterone Syst 2012 Mar
PMID:Gene polymorphisms of angiotensin-converting enzyme and angiotensin II type 1 receptor among chronic kidney disease patients in a Chinese population. 2214 63

The aim of the study was to describe the relationship of clinical outcome after percutaneous coronary intervention (PCI) with stenting and genetic polymorphisms (GP) which are known to relate to the incidence of in-stent restenosis and late thrombotic complications. The study included 190 patients with standardized clinical follow-up over 5 years, which were initially treated with PCI. We investigated clinical data, angiographic characteristics, 10 polymorphisms involved in neointimal hyperplasia and late thrombosis at 6 different levels and their relationship with the major adverse cardiac events (MACE). The long-term clinical outcome was defined by MACE: death, target vessel revascularization (PCI or coronary bypass grafting, CABG) and myocardial infarction. Angiotensin receptor type I (AGTR A1166C) and angiotensinogen (AGT MET235THR) GPs correlated with repeat revascularization and total MACE. Carriers of G allele for NOS3 A922G GP were shown to have a significantly lower repeat revascularization rate in comparison with the AA genotype, as did the T allele carriers in the NOS3 C690T GP analysis when compared to the CC genotype. The Asp genome carriers with the NOS3 GLU298ASP GP were also shown to have significantly less re-PCI in contrast to the Glu/Glu genotype. The study could document the protective influence of the 4G/5G GP for plasminogen inhibitor activator-1, which carried the lowest rate of re-PCI and total MACE during the follow-up. GPs for beta-1 G-protein subunit GNB3 C825T, fibrinogen FGB G455A and E-selectins Ser128Arg and Leu554Phe did not show statistical correlation with the clinical outcome. The results illustrate the potential use of genetic markers in defining patients with possibly worse clinical outcome after PCI, who may profit from more aggressive prevention of restenosis and late thrombotic complications.
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PMID:Relationship of genetic markers for atherosclerosis and long-term outcome after percutaneous coronary intervention with stenting. 2339 Aug 38

Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms (SNPs) in genes of the renin-angiotensin system (RAS) in a desert community of Indigenous Australians and in non-Indigenous Australians. The polymorphisms were angiotensinogen, AGT G-217A (rs5049); AGT G+174A (rs4762); Angiotensin II type 1 receptor, AGTR1 A+1166C (rs5186); angiotensin converting enzyme, ACE A-240T (rs4291), ACE T-93C (rs4292); renin, REN T+1142C (rs5706). They were measured using allelic discrimination assays. The prevalence of REN T+1142C SNP was similar in the two populations; 99% were homozygous for the T allele. All other SNPs were differently distributed between the two populations (P < 0.0001). In non-Indigenous Australians, the A allele at position 204 of ACE rs4291 was prevalent (61.8%) whereas in the Indigenous Australians the A allele was less prevalent (28%). For rs4292, the C allele had a prevalence of 37.9% in non-Indigenous Australians but in Indigenous Australians the prevalence was only 1%. No Indigenous individuals were homozygous for the C allele of AGTR1 (rs5186). Thus the prevalence of RAS SNPs in this Indigenous Australian desert community was different from non-Indigenous Australians as was the prevalence of cytokine SNPs (as shown in a previous study). These differences may affect susceptibility to chronic renal and cardiovascular disease and may alter the efficacy of drugs used to inhibit the RAS. These studies highlight the need to study the pharmacogenetics of drug absorption, distribution, metabolism and excretion in Indigenous Australians for safe prescribing guidelines.
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PMID:The prevalence of unique SNPs in the renin-angiotensin system highlights the need for pharmacogenetics in Indigenous Australians. 2666 52

The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages. Local BM RAS is important in hematopoietic stem cell biology and microenvironment. Angiotensin II regulates the proliferation, differentiation, and engraftment of hematopoietic stem cells. Activation of Mas receptor or ACE2 promotes proliferation of CD34+ cells. BM contains a progenitor that expresses renin throughout development. Angiotensin II attenuates the migration and proliferation of CD34+ Cells and promotes the adhesion of both MNCs and CD34+ cells. Renin cells in hematopoietic organs are precursor B cells. The renin cell requires RBP-J to differentiate. Mutant renin-expressing hematopoietic precursors can cause leukemia. Deletion of RBP-J in the renin-expressing progenitors enriches the precursor B-cell gene programme. Mutant cells undergo a neoplastic transformation, and mice develop a highly penetrant B-cell leukemia with multi-organ infiltration and early death. Many biological conditions during the development and function of blood cells are mediated by RAS, such as apoptosis, cellular proliferation, intracellular signaling, mobilization, angiogenesis, and fibrosis. The aim of this paper is to review recent developments regarding the actions of local BM RAS in the genesis of leukemia and other malignancies molecules.
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PMID:Local bone marrow renin-angiotensin system in the genesis of leukemia and other malignancies. 2777 88


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