| Cardiovascular consequences of genetic variation at -6/235 in human angiotensinogen using "humanized" gene-targeted mice. | |
| | |
MedLine Citation:
|
PMID: 20823378 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Genetic and functional data support a role for angiotensinogen in blood pressure control, and many population studies have suggested that polymorphisms in the angiotensinogen gene contribute to hypertension. Two common haplotypes of the human angiotensinogen gene are -6A/235T and -6G/235M. To study their contributions to blood pressure regulation in a controlled model system, we developed triple-transgenic mice expressing either -6A/235T or -6G/235M human angiotensinogen, expressing either an overexpressed and poorly regulated (REN9) or a tightly regulated (PAC160) human renin, and all carrying a null mutation in the endogenous murine angiotensinogen gene. These humanized mice were then examined for blood pressure differences at baseline and after a high-salt diet, changes in cardiovascular organ weight, and differences in angiotensinogen and renin gene expression. Mice expressing the -6G/235M haplotype on the PAC160 background exhibited increased blood pressure and cardiac hypertrophy at baseline. In contrast, all of the mice with the REN9 background had equivalent baseline blood pressures. On the REN9 background, there was a greater increase in blood pressure in -6A/235T in response to a high-salt diet, providing evidence it may be a susceptibility allele. There were no differences in angiotensinogen expression between haplotypes on either background strain. The data suggest that the impact of angiotensinogen haplotypes on cardiovascular end points may be dependent on renin status and environmental influences, such as dietary sodium. These insights may help explain the discrepancies among observational studies that have examined roles for the -6A/235T and -6G/235M angiotensinogen haplotypes in varied human populations. |
| | |
Authors:
|
Justin L Grobe; Matthew E Dickson; Sungmi Park; Deborah R Davis; Ella J Born; Curt D Sigmund |
Related Documents
:
|
11325068 - Lack of association between genetic polymorphism of cyp11b2 and hypertension in japanes... 11868598 - Water intake and 24-hour blood pressure monitoring in a patient with nephrogenic diabet... 1580808 - Decline in cognitive performance in aging twins. heritability and biobehavioral predict... 9171948 - Genetic factors associated with altered sodium transport in human hypertension: a twin ... 1449608 - Pressure profile along the oesophagus during eructation in sheep. 1352718 - Sympathoinhibitory effects of rilmenidine may be mediated by sites located below the br... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-07 |
Journal Detail:
|
Title: Hypertension Volume: 56 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-10-21 Completed Date: 2010-11-10 Revised Date: 2011-11-01 |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
|
Languages: eng Pagination: 981-7 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alleles Angiotensinogen / genetics*, metabolism Animals Blood Pressure / genetics* Genetic Variation Genotype Haplotypes Hypertension / genetics, metabolism Mice Mice, Transgenic Renin / genetics, metabolism Sodium, Dietary Telemetry |
| Grant Support | |
ID/Acronym/Agency:
|
DK007690/DK/NIDDK NIH HHS; HL048058/HL/NHLBI NIH HHS; HL061446/HL/NHLBI NIH HHS; HL084207/HL/NHLBI NIH HHS; HL098276/HL/NHLBI NIH HHS; K99 HL098276-01/HL/NHLBI NIH HHS; P01 HL062984-080005/HL/NHLBI NIH HHS; P01 HL062984-090005/HL/NHLBI NIH HHS; P01 HL084207-01A1/HL/NHLBI NIH HHS; P01 HL084207-01A10001/HL/NHLBI NIH HHS; P01 HL084207-02/HL/NHLBI NIH HHS; P01 HL084207-020001/HL/NHLBI NIH HHS; P01 HL084207-03/HL/NHLBI NIH HHS; P01 HL084207-030001/HL/NHLBI NIH HHS; P01 HL084207-04/HL/NHLBI NIH HHS; R01 HL061446-11/HL/NHLBI NIH HHS; R01 HL061446-12/HL/NHLBI NIH HHS; R01 HL061446-13/HL/NHLBI NIH HHS; R01 HL076421-04/HL/NHLBI NIH HHS; R37 HL048058-14/HL/NHLBI NIH HHS; R37 HL048058-15/HL/NHLBI NIH HHS; R37 HL048058-16/HL/NHLBI NIH HHS; R37 HL048058-17/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Sodium, Dietary; 11002-13-4/Angiotensinogen; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects on Peripheral and Central Blood Pressure of Cocoa With Natural or High-Dose Theobromine. A R...
Next Document: Endothelin-1 increases glomerular permeability and inflammation independent of blood pressure in the...