Evidence map›Paper›PMID 30084918›Full record

ArticleAmerican journal of hypertension2018

Age-Related Expression of Human AT1R Variants and Associated Renal Dysfunction in Transgenic Mice.

Sudhir Jain, Anita Rana, Kavita Jain, Sravan K Perla, Nitin Puri, Ashok Kumar

Open access · bronzeAbstract read
In one paragraph

Article in American journal of hypertension, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact, top 86% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Sudhir JainDepartment of Pathology, Basic Science Building, New York Medical College, Valhalla, New York, USA.
Anita RanaDepartment of Bioinformatics and Genomics, University of North Carolina, Charlotte, North Carolina, USA.
Kavita JainDepartment of Pathology, Basic Science Building, New York Medical College, Valhalla, New York, USA.
Sravan K PerlaDepartment of Pathology, Basic Science Building, New York Medical College, Valhalla, New York, USA.
Nitin PuriDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA.
Ashok KumarDepartment of Pathology, Basic Science Building, New York Medical College, Valhalla, New York, USA.
New York Medical College · USMarshall University · USUniversity of North Carolina at Charlotte · US

Funding

Non-Coding Variants of Angiotensinogen Gene and HypertensionR01HL130344 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI KUMAR, ASHOK · 2016 to 2019
$2.4M
Transcriptional regulation of human angiotensin receptorR01HL081752 · NHLBI · NEW YORK MEDICAL COLLEGE · PI KUMAR, ASHOK · 2006 to 2010
$1.9M
Transcriptional Regulation of Angiotensinogen GeneR01HL092558 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI KUMAR, ASHOK · 2009 to 2013
$1.9M
Genetics of HypertensionR01HL105113 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI KUMAR, ASHOK · 2011 to 2014
$1.5M
NHLBI NIH HHS R01 HL081752NHLBI NIH HHS R01 HL092558NHLBI NIH HHS R01 HL105113NHLBI NIH HHS R01 HL130344
6 · The paper itself

Abstract

backgroundThe contribution of single nucleotide polymorphisms in transcriptional regulation of the human angiotensin receptor type I (hAT1R) gene in age-related chronic pathologies such as hypertension and associated renal disorders is not well known. The hAT1R gene has single nucleotide polymorphisms in its promoter that forms 2 haplotypes (Hap), Hap-I and Hap-II. Hap-I of AT1R gene is associated with hypertension in Caucasians. We have hypothesized here that age will alter the transcriptional environment of the cell and will regulate the expression of hAT1R gene in a haplotype-dependent manner. This could likely make subjects with Hap-I increasingly susceptible to age-associated, AT1R-mediated complications.

methodWe generated transgenic (TG) mice with Hap-I and Hap-II. Adults (10-12 weeks) and aged (20-24 months) TG male mice containing either Hap-I or Hap-II were divided into 4 groups to study (i) the age-associated and haplotype-specific transcriptional regulation of hAT1R gene and (ii) their physiological relevance.

resultsIn aged animals, TG mice with Hap-I show increased expression of hAT1R and higher blood pressure (BP); suppression of antioxidant defenses (hemoxygenase, superoxide dismutase) and antiaging molecules (ATRAP, Klotho, Sirt3); increased expression of pro-inflammatory markers (IL-6, TNFα, CRP, NOX1); and increased insulin resistance. In vivo ChIP assay shows stronger binding of transcription factor USF2 to the chromatin of Hap-I mice.

conclusionOur results suggest that in aged animals, as compared with Hap-II, the TG mice with Hap-I overexpress hAT1R gene due to the stronger transcriptional activity, thus resulting in an increase in their BP and associated renal disorders.

Indexed as

Polymorphism, Single NucleotideAgingAnimalsBinding SitesBlood PressureGene Expression RegulationGenetic Predisposition to DiseaseHaplotypesHumansKidneyMaleMice, TransgenicPhenotypePromoter Regions, GeneticReceptor, Angiotensin, Type 1RNA Polymerase IIAGTR1 protein, humanReceptor, Angiotensin, Type 1RNA Polymerase IIUpstream Stimulatory FactorsUsf2 protein, mouse

Identifiers

PMID30084918
PMCPMC6454504
OpenAlexW2885382856

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.