Disease relevance of AGTR1

• OBJECTIVES: The present study aimed to assess the effect of haplotype variation in angiotensin II type I receptor (AGTR1) gene on the risk of myocardial infarction (MI) in Chinese males [1].
• CONCLUSIONS: The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis [2].
• There was also an increase in risk of hypertension associated with the AGTR1 T allele for African Americans (versus CC genotype: TC genotype, OR = 2.62 [95% CI: 1.46-4.72]; TT genotype, OR = 2.67 [95% CI: 1.51-4.74]) [3].
• There was no association between genetic polymorphism of ACE, AGT M235T and AGTR1 A1166C and susceptibility to lupus nephritis, nor histological activity and chronicity indices in renal biopsy among the patients studied [4].
• Haplotypes of the angiotensin II receptor genes AGTR1 and AGTR2 in women with normotensive pregnancy and women with preeclampsia [5].

Psychiatry related information on AGTR1

• In brain tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor recognition site levels were decreased by approximately 30% in putamen relative to the control patients whilst angiotensin AT2 receptor levels were increased by some 90% in the caudate nucleus relative to the control patients [6].
• CONCLUSIONS : Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments [7].

High impact information on AGTR1

• The AV3V region is well provided with angiotensinergic nerve endings and angiotensin AT1 receptors, the receptor type responsible for acute responses to ANG II, and it responds vigorously to the dipsogenic action of ANG II [8].
• The vasopressor angiotensin II regulates vascular contractility and blood pressure through binding to type 1 angiotensin II receptors (AT1; refs 1, 2) [9].
• Here we show that the AT1 receptor and the bradykinin (B2) receptor also communicate directly with each other [9].
• AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration [9].
• AT1 receptors mediate most known functions of angiotensin II, while AT2 receptors may be important developmentally [10].

Chemical compound and disease context of AGTR1

• The adenine/cytosine1166 (A/C1166) polymorphism of the angiotensin-II type 1 receptor (AGTR1) gene is presumed to be associated with mitral valve prolapse syndrome (MVPS) in Caucasians [11].
• METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months [12].
• METHODS: Patients with mild-to-moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind study to receive treatment with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan (n = 43), or the beta1-adrenergic receptor blocker atenolol (n = 43) [13].
• In the present study, we used skin fibroblasts of human hypertrophic scar, which expressed both AT1 and AT2 receptors, and observed that Ang II increased Akt phosphorylation and phosphoinositide 3 kinase (PI 3-K) activity [14].
• Angiotensin II regulates phosphoinositide 3 kinase/Akt cascade via a negative crosstalk between AT1 and AT2 receptors in skin fibroblasts of human hypertrophic scars [14].

Biological context of AGTR1

• Mean values of PWV were 11.6 +/- 2.7 m/s in AGTR1 AA homozygotes, 13.3 +/- 3.3 m/s in AC heterozygotes, and 15.3 +/- 4.3 m/s in CC homozygotes (P < .0001 and P < .00001 after adjustment for age and mean blood pressure, respectively) [15].
• CONCLUSIONS: These results suggest that in hypertensive but not normotensive subjects, the AGTR1 and ACE genotypes are involved in the regulation of aortic rigidity [15].
• RESULTS: There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups [2].
• Five genetic polymorphisms of the RAAS (ACE, AGTR1, AGT, CMA, CYP11B2) were analyzed in all patients and the results of genetic analysis were correlated to severity of AS and LVH to determine the importance of the polymorphisms for LVH [16].
• SNPs in the angiotensin II Type 1 receptor (AGTR1) and nitric oxide synthase 3 (NOS3) genes were significantly associated with CK activity [17].

Anatomical context of AGTR1

• We investigated the association of polymorphisms in the angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1) genes with increased intima-media thickness (IMT) and the presence of plaques in carotid arteries [18].
• METHODS: We examined polymorphisms of four genes (AGTR1, CYP11B2, ACE, CMA) in 101 patients who had follow-up coronary angiography due to symptoms 88 +/- 52 months after coronary artery bypass graft surgery [19].
• Following the extraction of genomic DNA from the leukocytes in the peripheral blood, angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M(235)T) and angiotensin II type 1 receptor (AGTR1 A(1166)C) genotypes were determined by the polymerase chain reaction [20].
• Immunohistochemical staining showed AGTR1 expression by lung fibroblasts in fibroblastic foci within biopsies of idiopathic pulmonary fibrosis [21].
• These experiments provide evidence for subtype-specific receptor sorting and internalization of Ang II and its AT1a receptor as a receptor-ligand complex, and they suggest that the sequestration of receptors into endosomes is in dynamic equilibrium with receptor cycling to the plasma membrane [22].

Associations of AGTR1 with chemical compounds

• 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) [23].
• 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) [23].
• Ang II actions on blood pressure regulation, water electrolyte balance, and hormone secretion are primarily mediated by AGTR1 [24].
• We analyzed cDNA and genomic clones encoding the human angiotensin II type-1 receptor, AT1 [25].
• Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage [26].

Physical interactions of AGTR1

• In the present study, we find that beta-arrestin formed a stable complex with the AT1AR tail in endocytic vesicles and that the internalization of this complex was dynamin dependent [27].
• AT1 and AT2 receptor binding were determined with the AT1 receptor antagonist losartan [28].
• Angiotensin receptor antagonists inhibit the renin angiotensin system at different levels from ACE inhibitors by selectively blocking the binding of angiotensin II to AT1 receptors [29].
• Angiotensin II stimulates human fetal mesangial cell proliferation and fibronectin biosynthesis by binding to AT1 receptors [30].
• It is a member of the G-protein coupled receptor superfamily with a minimal sequence homology with the AT1 receptor, responsible for the known effect of angiotensin II [31].

Regulatory relationships of AGTR1

• Angiotensin AT1 receptor upregulates expression of basic fibroblast growth factor, basic fibroblast growth factor receptor and coreceptor in human coronary smooth muscle cells [32].
• In contrast, small interfering RNA targeting HIF-1alpha inhibited hypoxia-induced ACE and AT1 expression [33].
• The carboxyl-terminal tails of these receptors contribute directly to this phenotype, since a beta2AR bearing the AT1AR tail acquired the capacity to stimulate beta-arrestin redistribution to endosomes, whereas this property was lost for an AT1AR bearing the beta2AR tail [27].
• Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes [34].
• The angiotensin II (Ang II) type 1 (AT1) receptor is highly expressed on juxtaglomerular (G) cells and is assumed to be involved in the negative short loop feedback regulation of renin secretion and in the suppression of Ang II-mediated JG cell proliferation and/or growth [35].

Other interactions of AGTR1

• Beta-arrestin- and dynamin-dependent endocytosis of the AT1 angiotensin receptor [36].
• In one informative family available for linkage analysis, FH-II does not segregate with either the AT1 gene or the CYP11B2 gene, or any other genetic defect in the chromosome 8q21-8qtel region [37].
• CONCLUSION: The AGT A-20C and AGTR1 A1166C genotypes may influence resting BP response to ST, such that C-allele carriers at each of these loci reduce their resting BP in response to ST to a greater extent than A homozygotes [38].
• Conversely, allocations of two human 3q markers (AGTR1 and IL12A) clearly excluded APC 3 [39].
• Patients were genotyped for the angiotensinogen (M235T), the angiotensin-converting enzyme (insertion/deletion [I/D]), the angiotensin II type 1 receptor (AGTR1 A1166C), and the NOS3 (G894T) genes [40].

Analytical, diagnostic and therapeutic context of AGTR1

• METHODS: ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls [2].
• METHODS: We genotyped the D/I polymorphism in the ACE gene, the C(-344)T polymorphism in the CYP11B2 gene, and the C(-535)T polymorphism in the AGTR1 gene among African American and Latino members of the Multiethnic Cohort Study (MEC) to determine their association with hypertension [3].
• Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter [41].
• Confocal microscopy using fluorescein-conjugated angiotensin II showed that overexpression of dynamin-1(K44A) and dynamin-2(K44A) isoforms likewise inhibited agonist-induced AT1 receptor endocytosis in CHO cells [36].
• METHODS: We investigated the impact of the ACE, AGT, AT1, and AT2 genotypes on renal allograft function in 148 patients (77 men, 71 women) who underwent transplantation over a 5-year period [42].

References