Affinage

AGT

Angiotensinogen · UniProt P01019

Round 2 corrected
Length
476 aa
Mass
52.1 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Angiotensinogen (AGT) is the obligate secreted precursor of the angiotensin peptide family and a central determinant of renin–angiotensin system (RAS) activity, blood pressure homeostasis, and tissue-level angiotensin II signaling. The M235T coding variant and G-6A promoter variant directly modulate plasma AGT levels and basal transcription rate, respectively, conferring genetic susceptibility to essential hypertension and preeclampsia (PMID:1394429, PMID:8513325, PMID:9120024). AGT transcription in hepatocytes is upregulated by IFN-γ through a STAT1-binding promoter element and is epigenetically tuned by DNA methylation at CEBP sites, while post-transcriptionally miR-29a and miR-149-5p target the AGT 3′UTR to suppress expression (PMID:16949687, PMID:33925539, PMID:32141427, PMID:28189547). Beyond classical renin-mediated cleavage—enhanced by the renin receptor at cell surfaces (PMID:12045255)—AGT is expressed in adipose tissue with a complete local RAS machinery and signals through downstream TGFβ/Smad2, PI3K/AKT/EMT, and JAK2/STAT3 pathways in inflammatory, fibrotic, and oncogenic contexts (PMID:9814470, PMID:33571918, PMID:36986671, PMID:32141427).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 High

    Establishing AGT as a genetic determinant of blood pressure answered whether angiotensinogen itself—not just downstream RAS components—could be rate-limiting for hypertension risk.

    Evidence Genetic linkage analysis of hypertensive sibships in two independent cohorts with plasma AGT quantification stratified by M235T genotype

    PMID:1394429

    Open questions at the time
    • Whether M235T is causal or in linkage disequilibrium with the true functional variant
    • Mechanism by which M235T alters AGT secretion or stability unresolved
  2. 1993 High

    Extension of the AGT T235 association to preeclampsia demonstrated that this variant predisposes to hypertensive disorders beyond essential hypertension, broadening the clinical significance of AGT variation.

    Evidence Genetic association study in independent Caucasian and Japanese cohorts of preeclamptic women

    PMID:8513325

    Open questions at the time
    • Molecular mechanism linking elevated AGT to placental pathology not defined
    • Whether preeclampsia risk is mediated by maternal or fetal AGT genotype unclear
  3. 1997 High

    Identification of the G-6A promoter variant as a functional cis-regulatory element resolved how a non-coding AGT variant directly alters transcription rate and nuclear protein binding, mechanistically linking promoter variation to plasma AGT levels.

    Evidence Promoter-reporter assays (luciferase/CAT) and EMSA with nuclear extracts in human cells, plus genetic association

    PMID:9120024

    Open questions at the time
    • Identity of the nuclear factor whose binding is altered at −6 not determined
    • Contribution of G-6A versus M235T in cis not fully disentangled
  4. 1998 High

    Demonstrating local AGT expression together with renin, ACE, and cathepsins in adipose tissue established that angiotensin II can be generated in a tissue-autonomous manner, independent of hepatic secretion.

    Evidence Northern blot, Western blot, RT-PCR with restriction verification in human adipocytes

    PMID:9814470

    Open questions at the time
    • Quantitative contribution of adipose-derived versus hepatic AGT to circulating angiotensin peptides unknown
    • Regulatory signals controlling adipose AGT expression not characterized
  5. 2002 High

    Discovery that the renin receptor enhances AGT-to-angiotensin I conversion fourfold upon renin binding provided a cell-surface mechanism amplifying local RAS activity and added a non-proteolytic signaling dimension (ERK1/2) to renin–AGT interaction.

    Evidence Expression cloning, radioligand binding, kinetic conversion assays, and ERK phosphorylation assays with confocal colocalization in mesangial cells

    PMID:12045255

    Open questions at the time
    • Whether the renin receptor alters AGT conformation or merely concentrates renin at the surface not resolved
    • In vivo contribution of receptor-bound versus soluble renin to AGT cleavage not quantified
  6. 2006 High

    Mapping a STAT1-binding element in the AGT promoter responsive to IFN-γ defined a cytokine-driven transcriptional pathway for AGT distinct from the known IL-6/STAT3 and glucocorticoid mechanisms, linking innate immune activation to RAS induction.

    Evidence Promoter deletion reporters, EMSA, ChIP, and site-directed mutagenesis in Hep3B hepatocytes

    PMID:16949687

    Open questions at the time
    • Whether STAT1-driven AGT induction occurs in non-hepatic tissues not tested
    • Physiological contexts in which IFN-γ-mediated AGT upregulation is rate-limiting for angiotensin II generation unknown
  7. 2017 Medium

    Identification of miR-29a and miR-149-5p as direct post-transcriptional repressors of AGT via its 3′UTR established a new regulatory layer, with functional consequences for retinal neovascularization (miR-29a) and chondrocyte inflammation through JAK2/STAT3 (miR-149-5p).

    Evidence Luciferase 3′UTR reporter with wild-type and mutant constructs (miR-149-5p); miR-29a overexpression/knockdown in diabetic retinopathy and OIR rodent models with AGT protein and angiogenic readouts; siRNA epistasis in chondrocytes

    PMID:28189547 PMID:28337307 PMID:32141427

    Open questions at the time
    • miR-29a targeting of AGT 3′UTR lacks direct luciferase validation in the cited study
    • Whether these miRNAs regulate hepatic AGT output in vivo not examined
    • Relative contribution of AGT suppression versus other targets of miR-29a to the anti-angiogenic phenotype unresolved
  8. 2017 Medium

    AGT-REN double transgenic mice demonstrated that sustained AGT/angiotensin II elevation drives myocardial fibrosis via ROS-mediated ERK1/2 activation of KCa3.1 channels, placing AGT upstream of oxidative-stress-dependent ion channel remodeling in cardiac fibroblasts.

    Evidence Double transgenic mouse model with pharmacological interventions (losartan, NAC, apocynin, PD98059, TRAM-34); Western blot and biochemical assays for pathway components

    PMID:28455747

    Open questions at the time
    • Whether KCa3.1 upregulation is a direct consequence of angiotensin II receptor signaling or secondary to ROS accumulation not fully dissected
    • Single lab; independent replication pending
  9. 2021 Medium

    Epigenetic regulation of AGT was defined by showing that DNA methylation at CEBP sites in the AGT promoter acts as an on/off switch: demethylation by high salt and aldosterone activates AGT transcription in adipose and cardiac tissue, linking dietary and hormonal inputs to epigenomic control of local RAS.

    Evidence Bisulfite sequencing and ChIP for CEBP binding in salt-sensitive hypertensive rats and human cardiac tissue

    PMID:33925539

    Open questions at the time
    • Causal relationship between demethylation and CEBP binding not established by interventional demethylation
    • Whether methylation changes are reversible upon salt restriction not tested
  10. 2021 Medium

    Placing AGT upstream of TGFβ/Smad2 signaling in diabetic nephropathy and demonstrating that AGT knockdown attenuates fibrotic responses in mesangial cells broadened AGT's effector role beyond hemodynamics to organ fibrosis.

    Evidence siRNA knockdown in high-glucose-stimulated mesangial cells with Western blot for TGFβ1/Smad2; in vivo validation in db/db mice treated with epiberberine

    PMID:33571918

    Open questions at the time
    • Whether fibrotic effect is mediated by angiotensin II or by intact AGT protein not distinguished
    • Specificity of epiberberine for AGT versus off-target effects not fully controlled
  11. 2021 High

    Antisense oligonucleotide-mediated AGT suppression in hypertensive humans validated AGT as a druggable therapeutic target, providing clinical proof-of-concept that reducing the precursor pool itself can modulate RAS activity.

    Evidence Phase 1 and Phase 2 double-blind placebo-controlled trials of IONIS-AGT-LRx with plasma AGT as pharmacodynamic endpoint

    PMID:34222719

    Open questions at the time
    • Long-term safety and blood-pressure efficacy not yet established in Phase 3 trials
    • Effect on tissue (non-hepatic) AGT pools not assessed
  12. 2023 Medium

    Demonstration that AGT knockdown impairs PI3K/AKT-mediated EMT in gastric cancer—rescued by a PI3K agonist—positioned AGT as an upstream activator of an oncogenic signaling axis and suggested AGT loss sensitizes tumors to 5-fluorouracil.

    Evidence siRNA knockdown with PI3K/AKT agonist rescue in GC cell lines; Western blot for EMT markers; xenograft tumor growth assay

    PMID:36986671

    Open questions at the time
    • Whether the oncogenic effect requires angiotensin II generation or is a direct property of AGT protein not resolved
    • Relevance to human gastric cancer in vivo beyond xenograft models not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether AGT exerts signaling functions independent of its cleavage to angiotensin peptides, and structural determinants of variant-specific differences in renin cleavage efficiency or secretion rate have not been defined.
  • No crystal structure of full-length human AGT in complex with renin to explain M235T kinetic differences
  • Angiotensin-independent functions of intact AGT protein not tested by cleavage-resistant mutants
  • Relative contribution of hepatic versus tissue-specific AGT to local and systemic angiotensin generation in humans not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-109582 Hemostasis 3 R-HSA-1643685 Disease 3
Partners
ACEATP6AP2RENSMAD2TGFB1

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Molecular variants of angiotensinogen (AGT), particularly M235T, are genetically linked to essential hypertension in two independent human cohorts, and plasma angiotensinogen concentrations differ significantly among hypertensive subjects with different AGT genotypes, establishing AGT as a genetic determinant of angiotensinogen levels and blood pressure. Genetic linkage analysis of hypertensive sibships + plasma angiotensinogen quantification stratified by genotype Cell High 1394429
1993 The T235 molecular variant of angiotensinogen is significantly associated with preeclampsia in Caucasian and Japanese women, corroborating and extending the link between AGT variants and hypertensive disorders of pregnancy. Genetic association study in two independent ethnically distinct cohorts (Caucasian and Japanese) Nature genetics High 8513325
1997 A common nucleotide substitution in the proximal AGT promoter (G-to-A at position −6 upstream of transcription initiation) is associated with essential hypertension and directly reduces basal transcription rate of the AGT gene, as demonstrated by promoter-reporter assays and electrophoretic mobility shift assays showing altered nuclear protein binding at this element. Promoter-reporter (luciferase/CAT) assays + EMSA with nuclear proteins; genetic association in hypertensive subjects The Journal of clinical investigation High 9120024
1998 Human adipose tissue expresses angiotensinogen mRNA and protein, as well as renin, angiotensin-converting enzyme, cathepsin D, and cathepsin G, establishing that angiotensinogen can be processed locally within adipose tissue to produce angiotensin II independently of the circulating renin-angiotensin system. Northern blot (angiotensinogen mRNA), Western blot (angiotensinogen protein in isolated adipocytes), RT-PCR + Southern blot (renin, ACE, cathepsin D, cathepsin G mRNAs) with restriction enzyme verification The Journal of clinical endocrinology and metabolism High 9814470
2000 The T235 allele of the AGT gene is associated with greater stimulation of plasma AGT secretion after ethinylestradiol administration in normotensive men, resulting in higher peak plasma AGT concentrations in TT versus MM homozygotes; the renin-angiotensin system readjusts through decreased renin release, blunting the physiological impact of elevated AGT. Controlled pharmacological challenge (ethinylestradiol ± furosemide/captopril) with plasma AGT, renin activity, and active renin measurements in TT vs MM homozygous men The Journal of clinical endocrinology and metabolism Medium 11095476
2002 The renin receptor binds renin and prorenin at the cell surface and, upon renin binding, increases the catalytic efficiency of angiotensinogen conversion to angiotensin I by fourfold, while also activating intracellular MAP kinase signaling (ERK1/ERK2 phosphorylation); the receptor is localized to mesangial glomerular cells and subendothelium co-localizing with renin. Expression cloning; radioligand binding assays; angiotensinogen conversion kinetic assays; phosphorylation/MAP kinase activation assays; confocal microscopy for colocalization The Journal of clinical investigation High 12045255
2006 IFN-γ upregulates AGT mRNA and promoter activity in hepatocytes through a STAT1-binding element located between −271 and −279 bp in the AGT promoter; EMSA and ChIP assays confirm IFN-γ–induced STAT1 binding to this element, and mutation of the STAT1 site in the full-length promoter reduces IFN-γ responsiveness, defining a pathway distinct from the IL-6/STAT3 or dexamethasone/GR mechanisms. Promoter deletion reporter assays, EMSA, chromatin immunoprecipitation (ChIP), site-directed mutagenesis of STAT1 element in hepatocytes (Hep3B) Biochimica et biophysica acta High 16949687
2017 AGT knockdown in IL-6-stimulated chondrocytes inhibits increases in IL-1β, MMP-13, and nitrite through blocking the renin-angiotensin system; miR-149-5p directly targets the AGT 3′UTR (validated by luciferase reporter and mutant constructs), suppressing AGT expression and thereby attenuating JAK2/STAT3 pathway activation and inflammatory responses in osteoarthritis chondrocytes. Loss-of-function siRNA knockdown; luciferase reporter assay with wild-type and mutant AGT 3′UTR; JAK2/STAT3 pathway inhibitor treatment; RT-qPCR and Western blot in IL-6-stimulated HC-a cells and OA patient cartilage Clinical and experimental rheumatology Medium 32141427
2017 miR-29a directly targets the AGT 3′UTR and negatively regulates AGT mRNA and protein expression in a rat diabetic retinopathy model; overexpression of miR-29a reduces AGT expression, vascular density, and retinal neovascularization, while knockdown of miR-29a has the opposite effect, establishing an miR-29a→AGT regulatory axis controlling retinal angiogenesis. qRT-PCR, Western blot, ADPase histochemical staining of retinal neovascularization, H&E staining; miR-29a overexpression and knockdown in DR rat model and AR42J cells Experimental and molecular pathology Medium 28189547
2017 miR-29a suppresses AGT mRNA and protein expression in oxygen-induced retinopathy mouse models; AGT knockdown via si-AGT phenocopies miR-29a overexpression, reducing VEGF, HGF, angiotensin, and angiotensin II protein levels and decreasing retinal neovascularization, placing AGT upstream of angiogenic factor production in ROP pathology. qRT-PCR, Western blot (AGT, VEGF, HGF, ANG, AngII), ADPase histochemical staining, H&E staining; miR-29a mimics/inhibitors and si-AGT in OIR mouse model American journal of translational research Medium 28337307
2017 In AGT-REN double transgenic hypertensive mice, elevated angiotensin II increases myocardial oxidative stress (elevated MDA, reduced SOD activity), which upregulates KCa3.1 channel protein expression via the ERK1/2 pathway, promoting cardiac fibroblast proliferation and myocardial fibrosis; blockade of ROS (NAC, apocynin) or ERK1/2 (PD98059) reduces KCa3.1 expression and fibrosis. AGT-REN double transgenic mouse model; TRAM-34/losartan/NAC/apocynin/PD98059 pharmacological interventions; Western blot (KCa3.1, p-ERK1/2, β-MHC); biochemical assays (MDA, SOD); histological collagen staining Pflugers Archiv : European journal of physiology Medium 28455747
2021 EPI (epiberberine) reduces AGT expression in glomerular mesangial cells and db/db diabetic mice, and AGT siRNA knockdown attenuates proliferation, G2/M arrest, and TGFβ1/Smad2 expression, establishing AGT as an upstream activator of the TGFβ/Smad2 fibrotic pathway in diabetic nephropathy; molecular docking and RNA-seq identified AGT as the key therapeutic target of EPI. RNA-seq of kidney tissue; molecular docking; siRNA knockdown in HG-stimulated glomerular mesangial cells; Western blot (AGT, TGFβ1, Smad2); in vivo db/db mouse treatment with histopathology and renal function assays Phytomedicine Medium 33571918
2021 DNA methylation at CCAAT-enhancer-binding-protein (CEBP) sites in the AGT promoter negatively regulates AGT expression; high salt intake and excess aldosterone cause DNA demethylation at these sites in visceral adipose tissue and heart, converting AGT expression from inactive to active state; low DNA methylation at CEBP-binding sites is associated with increased cardiac AGT expression in salt-sensitive hypertension. Bisulfite sequencing/methylation analysis of AGT promoter; ChIP for CEBP binding; comparison of salt-sensitive hypertensive rats vs controls; human cardiac tissue analysis International journal of molecular sciences Medium 33925539
2021 AGT promotes colorectal carcinoma cell proliferation, migration, invasion, and HUVEC angiogenesis (induced by CRC-conditioned medium); AGT expression correlates with isoliquiritigenin drug sensitivity, and ISL suppresses CRC progression in vitro. In vitro functional assays (proliferation, migration, invasion, angiogenesis) in CRC cell lines; conditional medium HUVEC angiogenesis assay; drug response analysis (CCLE, CTRP) International immunopharmacology Low 34655849
2021 Antisense oligonucleotide IONIS-AGT-LRx, administered subcutaneously, significantly reduces plasma angiotensinogen (AGT) protein levels in hypertensive humans in three separate controlled clinical trials, with a favorable safety profile and trends toward blood pressure reduction. Double-blind placebo-controlled Phase 1 and Phase 2 clinical trials; plasma AGT levels measured as pharmacodynamic endpoint JACC. Basic to translational science High 34222719
2023 AGT knockdown in gastric cancer cells reduces proliferation and migration, and impairs TGFβ/PI3K/AKT-mediated epithelial-mesenchymal transition (EMT); PI3K/AKT agonist 740Y-P rescues EMT impaired by AGT knockdown and 5-fluorouracil treatment, placing AGT upstream of PI3K/AKT→EMT signaling in gastric cancer and establishing that AGT loss enhances chemotherapy sensitivity in vitro and in vivo. siRNA knockdown of AGT in GC cell lines; Western blot (EMT markers, PI3K/AKT); PI3K/AKT agonist rescue experiment; in vivo xenograft tumor growth assay; bioinformatics risk signature from TCGA/GEO Pharmaceutics Medium 36986671

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation research 2338 10969042
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
1992 Molecular basis of human hypertension: role of angiotensinogen. Cell 1612 1394429
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2003 Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proceedings of the National Academy of Sciences of the United States of America 1398 12829792
2002 Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. The Journal of biological chemistry 1146 11815627
2002 Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. The Journal of clinical investigation 1101 12045255
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2018 The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiological reviews 828 29351514
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. The Biochemical journal 484 15283675
1997 A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. The Journal of clinical investigation 464 9120024
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2013 ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. British journal of pharmacology 426 23488800
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1993 A molecular variant of angiotensinogen associated with preeclampsia. Nature genetics 406 8513325
2001 Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. The Journal of biological chemistry 379 11707427
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2013 Discovery and characterization of alamandine: a novel component of the renin-angiotensin system. Circulation research 305 23446738
2003 WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Nature genetics 301 14608358
2008 NADPH oxidases and angiotensin II receptor signaling. Molecular and cellular endocrinology 300 19059306
2014 Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Kidney international 296 24694986
2005 Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circulation research 296 15718497
2003 Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II. Diabetes 295 12663475
1999 The renin-angiotensin-aldosterone system: a specific target for hypertension management. American journal of hypertension 288 10619573
2004 Renin-angiotensin system gene polymorphisms and atrial fibrillation. Circulation 281 15023884
1998 Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. The Journal of clinical endocrinology and metabolism 268 9814470
2004 DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nature structural & molecular biology 258 15221026
2000 Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding. The EMBO journal 175 10747039
2004 Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world. American journal of human genetics 103 15077204
2006 ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS. The European respiratory journal 84 17107992
2006 Primary hyperoxaluria type 1: AGT mistargeting highlights the fundamental differences between the peroxisomal and mitochondrial protein import pathways. Biochimica et biophysica acta 81 17027096
2005 The structure of the human AGT protein bound to DNA and its implications for damage detection. Journal of molecular biology 74 15964013
2021 Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx: Results of Phase 1 and Phase 2 Studies. JACC. Basic to translational science 71 34222719
2008 A two-step nucleotide-flipping mechanism enables kinetic discrimination of DNA lesions by AGT. Proceedings of the National Academy of Sciences of the United States of America 66 18353991
2002 Detection of putative functional angiotensinogen (AGT) gene variants controlling plasma AGT levels by combined segregation-linkage analysis. European journal of human genetics : EJHG 65 12404103
2000 AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study. American journal of physiology. Heart and circulatory physiology 64 10899077
2006 Fluorophores for live cell imaging of AGT fusion proteins across the visible spectrum. BioTechniques 57 16925018
1998 Diabetic nephropathy is associated with AGT polymorphism T235: results of a family-based study. Hypertension (Dallas, Tex. : 1979) 57 9461232
2017 Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 54 28760411
1992 Neocarzinostatin-mediated DNA damage in a model AGT.ACT site: mechanistic studies of thiol-sensitive partitioning of C4' DNA damage products. Biochemistry 52 1531616
2011 4-nitrobenzyloxycarbonyl derivatives of O(6)-benzylguanine as hypoxia-activated prodrug inhibitors of O(6)-alkylguanine-DNA alkyltransferase (AGT), which produces resistance to agents targeting the O-6 position of DNA guanine. Journal of medicinal chemistry 43 21955333
2009 The C allele of the AGT Met235Thr polymorphism is associated with power sports performance. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 42 20029521
2006 Interactions of human O6-alkylguanine-DNA alkyltransferase (AGT) with short single-stranded DNAs. The Journal of biological chemistry 37 17138560
2004 Adipose angiotensinogen secretion, blood pressure, and AGT M235T polymorphism in obese patients. Obesity research 37 15044674
2008 Blood pressure and interactions between the angiotensin polymorphism AGT M235T and sodium intake: a cross-sectional population study. The American journal of clinical nutrition 36 18689375
2021 Endogenous tRNA-derived small RNA (tRF3-Thr-AGT) inhibits ZBP1/NLRP3 pathway-mediated cell pyroptosis to attenuate acute pancreatitis (AP). Journal of cellular and molecular medicine 35 34643045
2013 Association of rs699 (M235T) polymorphism in the AGT gene with power but not endurance athlete status. Journal of strength and conditioning research 33 23287839
2003 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition. Cancer chemotherapy and pharmacology 31 14704831
2020 AGT, targeted by miR-149-5p, promotes IL-6-induced inflammatory responses of chondrocytes in osteoarthritis via activating JAK2/STAT3 pathway. Clinical and experimental rheumatology 29 32141427
2002 Differential responses of EGFR-/AGT-expressing cells to the "combi-triazene" SMA41. Cancer chemotherapy and pharmacology 29 12497201
2021 DNA Methylation of the Angiotensinogen Gene, AGT, and the Aldosterone Synthase Gene, CYP11B2 in Cardiovascular Diseases. International journal of molecular sciences 27 33925539
2002 Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1 R and ecNOS. Clinical nephrology 27 11926202
1996 Allele-specific PCR analysis of p53 codon 249 AGT transversion in liver tissues from patients with viral hepatitis. International journal of cancer 27 8895534
2008 The M235T polymorphism in the AGT gene and CHD risk: evidence of a Hardy-Weinberg equilibrium violation and publication bias in a meta-analysis. PloS one 26 18575631
2011 Gender-related association of AGT gene variants (M235T and T174M) with essential hypertension--a case-control study. Clinical and experimental hypertension (New York, N.Y. : 1993) 25 22148914
2008 Interactions of human O(6)-alkylguanine-DNA alkyltransferase (AGT) with short double-stranded DNAs. Biochemistry 25 19061338
2001 Overexpression of human O6-alkylguanine DNA alkyltransferase (AGT) prevents MNU induced lymphomas in heterozygous p53 deficient mice. Oncogene 24 11536039
2011 Haplotype-based association of ACE I/D, AT1R 1166A>C, and AGT M235T polymorphisms in renin-angiotensin-aldosterone system genes in Korean women with idiopathic recurrent spontaneous abortions. European journal of obstetrics, gynecology, and reproductive biology 23 21636204
2015 Increased urinary Angiotensinogen/Creatinine (AGT/Cr) ratio may be associated with reduced renal function in autosomal dominant polycystic kidney disease patients. BMC nephrology 22 26092580
2005 Structural evidence of a passive base-flipping mechanism for AGT, an unusual GT-B glycosyltransferase. Journal of molecular biology 22 16081100
2021 Epiberberine ameliorated diabetic nephropathy by inactivating the angiotensinogen (Agt) to repress TGFβ/Smad2 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 21 33571918
2016 The AGT Gene M235T Polymorphism and Response of Power-Related Variables to Aerobic Training. Journal of sports science & medicine 21 27928207
2014 A polymorphism in AGT and AGTR1 gene is associated with lead-related high blood pressure. Journal of the renin-angiotensin-aldosterone system : JRAAS 21 25031294
2010 Associations between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the Multi-ethnic Study of Atherosclerosis. American journal of nephrology 21 20606419
2008 Gender-dependent effect of ACE I/D and AGT M235T polymorphisms on the progression of urinary albumin excretion in Taiwanese with type 2 diabetes. American journal of nephrology 21 18849600
2017 Role of microRNA-29a in the development of diabetic retinopathy by targeting AGT gene in a rat model. Experimental and molecular pathology 20 28189547
2017 Oxidative stress promotes myocardial fibrosis by upregulating KCa3.1 channel expression in AGT-REN double transgenic hypertensive mice. Pflugers Archiv : European journal of physiology 20 28455747
2012 Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis. Journal of assisted reproduction and genetics 20 22644634
2006 Upregulation of human angiotensinogen (AGT) gene transcription by interferon-gamma: involvement of the STAT1-binding motif in the AGT promoter. Biochimica et biophysica acta 20 16949687
2005 Haplotype association analysis of AGT variants with hypertension-related traits: the HyperGEN study. Human heredity 20 16352906
2021 Epigenetics and expression of key genes associated with cardiac fibrosis: NLRP3, MMP2, MMP9, CCN2/CTGF and AGT. Epigenomics 19 33538177
2014 Genetic variants of ACE (Insertion/Deletion) and AGT (M268T) genes in patients with diabetes and nephropathy. Journal of the renin-angiotensin-aldosterone system : JRAAS 18 24737640
2000 Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration. The Journal of clinical endocrinology and metabolism 18 11095476
2011 Association of polymorphisms in the AGT gene with essential hypertension in the Chinese population. Journal of the renin-angiotensin-aldosterone system : JRAAS 17 22156763
2013 AGT M235T polymorphisms and ischemic stroke risk: a meta-analysis. Journal of the neurological sciences 16 23790236
2013 Occurrence of multiple chloroquine-resistant Pfcrt haplotypes and emergence of the S(agt)VMNT type in Cameroonian Plasmodium falciparum. The Journal of antimicrobial chemotherapy 16 24092656
2012 Association of AGT M235T and ACE I/D polymorphisms with the risk of ischemic stroke: meta-analysis in Han Chinese population. Journal of the neurological sciences 16 22800767
2006 Sequence variants of ACE, AGT, AT1R, and PAI-1 as genetic risk factors for vascular dementia. Neuroscience letters 16 16603315
2021 Linkage of blood pressure, obesity and diabetes mellitus with angiotensinogen gene (AGT 704T>C/rs699) polymorphism in hypertensive patients. Bratislavske lekarske listy 15 34570572
2015 Angiotensinogen (AGT) M235T, AGT T174M and Angiotensin-1-Converting Enzyme (ACE) I/D Gene Polymorphisms in Essential Hypertension: Effects on Ramipril Efficacy. The open cardiovascular medicine journal 15 27006715
2011 Mutagenicity associated with O6-methylguanine-DNA damage and mechanism of nucleotide flipping by AGT during repair. Physical biology 15 21666294
2010 Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data. BMC medical genetics 15 20537141
2009 Multilocus analysis in candidate genes ACE, AGT, and AGTR1 and predisposition to peripheral arterial disease: role of ACE D/-240T haplotype. Journal of vascular surgery 15 19782519
2007 The C-532T polymorphism of the angiotensinogen gene is associated with pulse pressure: a possible explanation for heterogeneity in genetic association studies of AGT and hypertension. International journal of epidemiology 15 17998241
2003 Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population. Journal of human hypertension 15 12874613
2018 NBGNU: a hypoxia-activated tripartite combi-nitrosourea prodrug overcoming AGT-mediated chemoresistance. Future medicinal chemistry 14 30560688
2005 New Anastomosis Groups, AG-T and AG-U, of Binucleate Rhizoctonia spp. Causing Root and Stem Rot of Cut-Flower and Miniature Roses. Phytopathology 14 18943011
2021 AGT serves as a potential biomarker and drives tumor progression in colorectal carcinoma. International immunopharmacology 13 34655849
2019 An AGT-based protein-tag system for the labelling and surface immobilization of enzymes on E. coli outer membrane. Journal of enzyme inhibition and medicinal chemistry 13 30724623
2011 Epistatic effects of ACE I/D and AGT gene variants on left ventricular mass in hypertensive patients: the HyperGEN study. Journal of human hypertension 13 21248783
2010 Frequency of the AGT Pro11Leu polymorphism in humans: Does diet matter? Annals of human genetics 13 20059472
2002 AGT and AT1R gene polymorphism in hypertensive heart disease. International journal of clinical practice 13 12425365
2012 Effect of GPE-AGT nanoparticle shRNA transfection system mediated RNAi on early atherosclerotic lesion. International journal of clinical and experimental pathology 12 22977667
2010 The angiotensinogen AGT p.M235T gene polymorphism may be responsible for the development of severe anaphylactic reactions to insect venom allergens. International archives of allergy and immunology 12 20413984
2023 Hypoxia and CD44 receptors dual-targeted nano-micelles with AGT-inhibitory activity for the targeting delivery of carmustine. International journal of biological macromolecules 11 37399878
2022 Associations between AGT, MTHFR, and VEGF gene polymorphisms and preeclampsia in the Chinese population. Placenta 11 35030476
2017 Effects of microRNA-29a on retinopathy of prematurity by targeting AGT in a mouse model. American journal of translational research 11 28337307
2017 Associations of high altitude polycythemia with polymorphisms in EPHA2 and AGT in Chinese Han and Tibetan populations. Oncotarget 11 28881807
2008 The M235T polymorphism of the AGT gene modifies the risk of coronary artery disease associated with the presence of hypercholesterolemia. European journal of epidemiology 11 18409009
2005 Context-dependency of the relation between left ventricular mass and AGT gene variants. Journal of human hypertension 11 15483663
2025 Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease. Science advances 10 40203111
2019 The correlation between AGT gene polymorphism and neonatal hypoxic-ischemic encephalopathy (HIE). European review for medical and pharmacological sciences 10 30915766
2012 The interaction of AGT and NOS3 gene polymorphisms with conventional risk factors increases predisposition to hypertension. Journal of the renin-angiotensin-aldosterone system : JRAAS 10 22791701
2010 COC use, ACE/AGT gene polymorphisms, and risk of stroke. Pharmacogenetics and genomics 10 20300047
2004 AGT and RH blood group polymorphisms affect blood pressure and lipids in Afro-Caribbeans. Journal of human hypertension 10 14961043
1993 Linkage of Agt and Actsk-1 to distal mouse chromosome 8 loci: a new conserved linkage. Mammalian genome : official journal of the International Mammalian Genome Society 10 8093670
2021 Myocardial Infarction and AGT p.Thr174Met Polymorphism: A Meta-Analysis of 7657 Subjects. Cardiovascular therapeutics 9 34025779
2020 Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population. Journal of the renin-angiotensin-aldosterone system : JRAAS 9 32356512
2015 Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis. Genetics and molecular research : GMR 9 26125750
2010 AGT genetic variation, plasma AGT, and blood pressure: An analysis of the Utah Genetic Reference Project pedigrees. American journal of hypertension 9 20414195
2024 Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease. Frontiers in immunology 8 39308860
2023 System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy. Pharmaceutics 8 36986671
2023 The Role of AGT, AMPD1, HIF1α, IL-6 Gene Polymorphisms in the Athletes' Power Status: A Meta-Analysis. Journal of human kinetics 8 38053960
2021 Development and biological evaluation of AzoBGNU: A novel hypoxia-activated DNA crosslinking prodrug with AGT-inhibitory activity. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 8 34678728
2019 Prenatal Diagnosis of Autosomal Recessive Renal Tubular Dysgenesis with Anhydramnios Caused by a Mutation in the AGT Gene. Diagnostics (Basel, Switzerland) 8 31718018
2019 AGT rs699 and AGTR1 rs5186 gene variants are associated with cardiovascular-related phenotypes in atherosclerotic peripheral arterial obstructive disease. Irish journal of medical science 8 31858452
2017 Overexpression of AGT promotes bronchopulmonary dysplasis via the JAK/STAT signal pathway. Oncotarget 8 29221188
2015 Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis. Blood pressure 8 26556555
2015 Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample. Genetics and molecular research : GMR 8 26782563
2014 Association of AGT M235T gene polymorphism with HSP/HSPN risk. Renal failure 8 25350836
2013 Delivery of therapeutic AGT shRNA by PEG-Bu for hypertension therapy. PloS one 8 23894329
2013 Simple renal cysts and hypertension are associated with angiotensinogen (AGT) gene variant in Shiraz population (Iran). Journal of the renin-angiotensin-aldosterone system : JRAAS 8 23907112
1999 Association between AGT T235 variant and microalbuminuria in Canadian Oji-Cree with type 2 diabetes mellitus. Clinical biochemistry 8 10383081
2015 Association of polymorphisms in the AGT gene(M235T, T174M) with ischemic stroke in the Chinese population. Journal of the renin-angiotensin-aldosterone system : JRAAS 7 25944852
2013 CYP1A1, GCLC, AGT, AGTR1 gene-gene interactions in community-acquired pneumonia pulmonary complications. Molecular biology reports 7 24068433
2011 Association between the M235T polymorphism of the AGT gene and cytokines in patients with hypertension. Experimental and therapeutic medicine 7 22969920