Disease relevance of AGT

• The AGT mRNA and AT1 receptor mRNA levels were significantly higher in VAT than in SAT; AGT mRNA levels were higher, although not significantly, in overweight subjects in both SAT and VAT [1].
• Overexpression of adenovirus 12S E1A, which binds and inactivates p300/CBP, strongly inhibited basal and stimulated hAGT transcription, whereas a mutant E1A defective in binding p300/CBP did not [2].
• The T235 allele of the angiotensinogen (AGT) gene is associated with plasma AGT concentration and pregnancy-induced hypertension [3].
• We showed a relationship between mRNA expression of AGT and TGF-beta1 in kidney transplant patients with different grades of CAN and proteinuria [4].
• Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells [5].
• In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival [6].

Psychiatry related information on AGT

• The current results suggested that AGT T235M polymorphism might be a risk factor of vascular dementia [7].
• We sought to determine whether the M235T angiotensinogen (AGT) polymorphism, either interacting with habitual physical activity (PA) levels or independently, was associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise [8].
• The AGT T235 allele does not appear to be a marker for blood pressure variation in this group, but variants on chromosome 1q lying in or near the AGT gene may contribute to individual differences in the blood pressure response to ACE inhibition [9].
• In this cross-sectional study, we examined the association between functional polymorphisms in the angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in 115 bipolar affective disorder (BPAD) patients and 323healthy control subjects [10].
• The reason of this is not clear, but from the above mentioned seemingly indispensable association of grass-eating with the peroxisomal localization of SPT/AGT it may be related, at least in part, to the food habit of Japanese, especially that of old generation, that they prefer boiled greens rather than frying or raw vegetables [11].

High impact information on AGT

• The corroboration and replication afforded by these results support the interpretation that molecular variants of AGT constitute inherited predispositions to essential hypertension in humans [12].
• However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes [13].
• Our results suggest that polymorphisms at the AGT and ACE gene loci are important markers for predicting progression to chronic renal failure in Caucasian patients with IgA nephropathy [14].
• Similarly, patients with AGT MT and TT genotypes had higher maximal values of proteinuria than those with the MM genotype (i.e., median values, 2.5 and 3.5 vs. 2.0 g/d, respectively; P < 0.02 by Kruskal-Wallis test) [14].
• Multivariant analysis, however, detected an interaction between the AGT and ACE gene polymorphisms with the presence of ACE/DD polymorphism adversely affecting disease progression only in patients with the AGT/MM genotype (P = 0.008) [14].

Chemical compound and disease context of AGT

• Several polymorphisms of genes encoding for components of the renin angiotensin system such as the angiotensin converting enzyme (ACE), the angiotensinogen (AGT) gene, and the angiotensin II type 1 receptor (ATIR) have been associated with the development of pulmonary hypertension [15].
• Finally, angiotensinogen (AGT) genotype effects renal and adrenal responses to Ang II in patients with hypertension [16].
• The angiotensinogen (AGT) gene polymorphism M235T (a methionine to threonine amino acid substitution) has been investigated in association with essential hypertension (EHT) based on conventional measurement of blood pressure (BP); however, the results have been inconsistent [17].
• The frequency distribution of AGT M/T genotype did not differ between patients with malignant and non-malignant hypertension [18].
• We compared resistance to the methylating agent temozolomide (TMZ) and to the chloroethylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with and without AGT inhibition by 06-bG in several colorectal carcinoma cell lines [19].

Biological context of AGT

• Angiotensin II, a potent vasoactive peptide produced by proteolysis of the angiotensinogen (AGT) prohormone, plays a critical role in cardiovascular homeostasis [2].
• Here, we tested the hypothesis that glial-derived AGT plays an important role in blood pressure regulation in hypertensive mice carrying human renin (hREN) and human AGT transgenes under the control of their own endogenous promoters [20].
• RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis [21].
• This promoter targets expression of transgene products to astrocytes, the most abundant cell type expressing AGT in brain [22].
• Because of the inability to dissect the functional role of astrocyte- vs. neuron-derived AGT in vivo by pharmacological approaches, the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and fluid and electrolyte balance remains unclear [23].

Anatomical context of AGT

• Angiotensinogen (AGT) is mainly expressed in glial cells in close proximity to renin-expressing neurons in the brain [20].
• The angiotensinogen gene (AGT) is a thrifty gene which increases the risk for common disease with growth of civilization via sodium and body fluid retention [24].
• In the brain, angiotensinogen (AGT) is expressed in astrocytes and in some neurons important to cardiovascular control, but its functional role remains undefined [22].
• In one line examined in detail, transgene expression was high in brain and low in tissues outside the central nervous system, and the level of plasma hAGT was not elevated over baseline [22].
• RESULTS: Human renal proximal tubule epithelial cells bound (125)I-AGT in a time-dependent manner [25].

Associations of AGT with chemical compounds

• Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques [26].
• Blood pressure in the hREN/GFAP-hAGT mice was lowered after ICV, but not intravenous losartan [22].
• Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration [3].
• The observed allele frequencies were: DD 31%, DI 41% and II 28%, for ACE; MM 42%, MT 37% and TT 21%, for the methionine (Met)235-->threonine (Thr) polymorphism of AGT; and AA 51%, AC 38% and CC 11%, for the adenine (A)1166-->cytosine (C) gene polymorphism [27].
• There were no statistically significant differences for AGT, ACE, and ATR1 polymorphisms with regard to the slope of 1/creatinine before renal Tx [27].

Physical interactions of AGT

• Upregulation of human angiotensinogen (AGT) gene transcription by interferon-gamma: Involvement of the STAT1-binding motif in the AGT promoter [28].
• A substitution (M235T) polymorphism in angiotensinogen (AGT) may interact with ACE I/D polymorphism for the risk of diabetic nephropathy, but their prognostic values have to be established by follow-up studies [29].
• We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217 [30].

Enzymatic interactions of AGT

• Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA [31].

Regulatory relationships of AGT

• IFN gamma treatment up-regulated AGT mRNA level and promoter activity in Hep3B hepatocytes [28].
• METHODS: Genotyping for the G460W-ADD, M235T-AGT and the insertion/deletion (I/D)-ACE gene polymorphisms was performed in 260 control subjects and 260 ESRD patients using polymerase chain reaction, gel analysis and appropriate restriction digest [32].
• ACE and AGT genes did not display any difference in clinical or metabolic parameters according to each gene's genotype for either the control or the NIDDM group [33].

Other interactions of AGT

• Conversely, ectopic expression of p300 and CBP potentiated inducible hAGT promoter activity [2].
• Taken together, our results indicate that IL-6-inducible expression of the hAGT promoter is mediated by physical association of the COOH terminus of STAT3 with p300/CBP, the recruitment of which targets histone acetylation and results in chromatin remodeling [2].
• Angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), angiotensin converting enzyme (ACE) mRNA, and protein levels were measured by reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively [1].
• AGT M235T and NOS3 A(-922)G and E298D polymorphisms were significantly associated with insulin sensitivity (P=0.018, 0.036, 0.039) but were not significant after adjusting for body mass index [34].
• Finally, treatment of HepG2 cells with a histone deacetylase inhibitor increased the hAGT mRNA abundance by 2- to 3-fold [2].

Analytical, diagnostic and therapeutic context of AGT

• The presence of AGT and ATI receptor in SAT and VAT was confirmed by Western blot analysis [1].
• Immunohistochemistry revealed a loss of AGT immunostaining glial cells throughout the brain in RAC mice [20].
• The terminal half-life (T1/2beta) was increased (130 versus 82 minutes) and the metabolic clearance rate (MCR) was decreased (0.83+/-0.29 versus 2.2+/-0.66 microL. min(-1). g(-1)) in the high hAGT strain compared with the low hAGT strain [35].
• The control group showed AGT levels of 25+/-12.2 pg/microg total RNA and TGF-beta1 levels of 228+/-111 transcripts/microg total RNA, significant only for the higher proteinuria group (P=0.01 and P=0.04, respectively) [4].
• Angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor and angiotensinogen (AGT) gene polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) [36].

References