Home LiteratureArticle Details
PMID: 9294106 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Angiotensinogen T235 expression is elevated in decidual spiral arteries.

The Journal of clinical investigation ·Vol. 100 ·No. 6 ·1997-09-15 ·Pages 1406-15

Morgan T, Craven C, Nelson L, Lalouel JM, Ward K

Abstract

Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.

MeSH Terms
Alleles Angiotensinogen/genetics,metabolism Female Heterozygote Humans Immunohistochemistry Muscle, Smooth, Vascular/metabolism Mutation Polymerase Chain Reaction Pre-Eclampsia/genetics Pregnancy Promoter Regions, Genetic RNA/analysis RNA, Messenger/analysis Trophoblasts/metabolism Uterus/blood supply,metabolism
Chemicals
RNA, Messenger Angiotensinogen RNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Morgan T
Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112, USA.
Craven C
Nelson L
Lalouel J M
Ward K
References (46)
46 references, click to expand
  1. Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter.
    J Biol Chem. 1990 May 5;265(13):7576-82 PMID: 1692023
  2. Fundamental principles of in situ hybridization.
    J Histochem Cytochem. 1993 Dec;41(12):1725-33 PMID: 8245419
  3. Kinetics of the renin system. The basis for determination of the different components of the system.
    Scand J Clin Lab Invest Suppl. 1973;132:3-86 PMID: 4358365
  4. Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells.
    J Clin Invest. 1989 Apr;83(4):1419-24 PMID: 2649516
  5. Alterations in uteroplacental blood flow precede hypertension in preeclampsia at high altitude.
    J Appl Physiol (1985). 1995 Jul;79(1):15-22 PMID: 7559213
  6. Trophoblastic invasion of human decidua from 8 to 18 weeks of pregnancy.
    Placenta. 1980 Jan-Mar;1(1):3-19 PMID: 7443635
  7. Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen.
    Science. 1996 Nov 8;274(5289):995-8 PMID: 8875944
  8. Vascular changes of endometrium in early pregnancy.
    Am J Clin Pathol. 1984 Jun;81(6):702-7 PMID: 6233900
  9. Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction.
    J Clin Invest. 1993 May;91(5):2058-64 PMID: 8387539
  10. Molecular mechanisms of vascular renin-angiotensin system in myointimal hyperplasia.
    Hypertension. 1991 Oct;18(4 Suppl):II100-5 PMID: 1916996
  11. Distribution of plasma angiotensin I-converting enzyme levels in healthy men: relationship to environmental and hormonal parameters.
    J Lab Clin Med. 1991 Jan;117(1):33-9 PMID: 1846167
  12. Preeclampsia: an endothelial cell disorder.
    Am J Obstet Gynecol. 1989 Nov;161(5):1200-4 PMID: 2589440
  13. Quantitative analysis of messenger RNA levels: reverse transcription-polymerase chain reaction single nucleotide primer extension assay.
    Methods Enzymol. 1993;225:344-51 PMID: 7694041
  14. Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy.
    Placenta. 1983 Oct-Dec;4(4):397-413 PMID: 6634666
  15. Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.
    J Clin Invest. 1991 Apr;87(4):1300-11 PMID: 2010543
  16. Molecular basis of human hypertension: role of angiotensinogen.
    Cell. 1992 Oct 2;71(1):169-80 PMID: 1394429
  17. Uterine artery Doppler flow velocity waveforms in the second trimester for the prediction of preeclampsia and fetal growth retardation.
    Obstet Gynecol. 1994 Mar;83(3):378-86 PMID: 8127529
  18. Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels.
    J Clin Endocrinol Metab. 1994 Jan;78(1):216-24 PMID: 8288707
  19. Problems associated with toxemia in twin pregnancies.
    Am J Obstet Gynecol. 1957 Jan;73(1):37-42 PMID: 13381795
  20. Molecular diagnosis of familial adenomatous polyposis.
    N Engl J Med. 1993 Dec 30;329(27):1982-7 PMID: 8247073
  21. Lesions of toxemia in first trimester pregnancies.
    Am J Clin Pathol. 1973 Mar;59(3):344-9 PMID: 4687351
  22. Circulating and tissue angiotensin systems.
    J Clin Invest. 1987 Jan;79(1):1-6 PMID: 3025255
  23. Vascular changes in the decidua associated with eclamptogenic toxemia of pregnancy.
    Am J Clin Pathol. 1950 Dec;20(12):1099-1109 PMID: 14783095
  24. Current topic: pre-eclampsia and the placenta.
    Placenta. 1991 Jul-Aug;12(4):301-8 PMID: 1946241
  25. Angiotensinogen: a candidate gene involved in preeclampsia?
    Nat Genet. 1993 Jun;4(2):114-5 PMID: 8348146
  26. A molecular variant of angiotensinogen associated with preeclampsia.
    Nat Genet. 1993 May;4(1):59-61 PMID: 8513325
  27. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.
    J Clin Invest. 1997 Apr 1;99(7):1786-97 PMID: 9120024
  28. Metabolic clearance rate of dehydroisoandrosterone sulfate. VI. Studies of eclampsia.
    Obstet Gynecol. 1976 Mar;47(3):327-30 PMID: 129717
  29. The role of the spiral arteries in the pathogenesis of preeclampsia.
    Obstet Gynecol Annu. 1972;1:177-91 PMID: 4669123
  30. Molecular variant of angiotensinogen gene is associated with coronary atherosclerosis.
    Circulation. 1995 Feb 15;91(4):951-4 PMID: 7850980
  31. Structure of human angiotensinogen gene.
    DNA. 1989 Mar;8(2):87-99 PMID: 2924688
  32. Morphology of placental villi after premature delivery and its clinical relevance.
    Arch Gynecol. 1986;239(2):101-14 PMID: 3777991
  33. Pregnancy in the sisters and daughters of eclamptic women.
    Pathol Microbiol (Basel). 1961;24:662-6 PMID: 13878803
  34. The physiological response of the vessels of the placental bed to normal pregnancy.
    J Pathol Bacteriol. 1967 Apr;93(2):569-79 PMID: 6054057
  35. Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy.
    Diabetes. 1996 Mar;45(3):367-369 PMID: 8593944
  36. [A case-control study of pregnancy-induced hypertension with a genetic predisposition: association of a molecular variant of angiotensinogen in the Japanese women].
    Hokkaido Igaku Zasshi. 1995 Jul;70(4):649-57 PMID: 7590609
  37. Placental bed spiral arteries in the hypertensive disorders of pregnancy.
    Br J Obstet Gynaecol. 1991 Jul;98(7):648-55 PMID: 1883787
  38. Pre-eclampsia and the angiotensinogen gene.
    Br J Obstet Gynaecol. 1995 Jun;102(6):489-90 PMID: 7632643
  39. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury.
    Science. 1989 Jul 14;245(4914):186-8 PMID: 2526370
  40. Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection.
    Nucleic Acids Res. 1993 Aug 11;21(16):3623-9 PMID: 8367277
  41. Biochemistry and regulation of angiotensinogen.
    Clin Exp Hypertens A. 1983;5(7-8):1005-19 PMID: 6640961
  42. Antigenic identification of cells in spiral artery trophoblastic invasion: validation of histologic studies by triple-antibody immunocytochemistry.
    Am J Obstet Gynecol. 1994 Jul;171(1):165-71 PMID: 8030693
  43. A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene.
    J Biol Chem. 1996 Jul 5;271(27):15981-6 PMID: 8663141
  44. Angiotensinogen.
    Fed Proc. 1983 Jul;42(10):2724-8 PMID: 6862036
  45. Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells.
    Hypertension. 1989 Apr;13(4):305-14 PMID: 2466788
  46. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples.
    Biotechniques. 1993 Sep;15(3):532-4, 536-7 PMID: 7692896
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119661
Published
1997-09-15
Pages
1406-15
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508319
Subset
IM
Grants
NICHD NIH HHS · 1R01-HD 32170-01 · United States
External Links
PubMed source DOI: 10.1172/JCI119661 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2