Evidence map›Paper›PMID 17644577›Full record

Trial reportAmerican journal of physiology. Heart and circulatory physiology2007

NFKB1 promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives.

Joon-Young Park, Iain K G Farrance, Nicola M Fenty, James M Hagberg, Stephen M Roth, David M Mosser, Min Qi Wang, Hanjoong Jo, Toshihiko Okazaki, Steven R Brant and 1 more

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in American journal of physiology. Heart and circulatory physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 19% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
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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

11 authors at 4 institutions in 1 country.

Joon-Young ParkDepartment of Kinesiology, College of Health Professions, Temple University, Philadelphia, Pennsylvania 19122, USA.
Iain K G Farrance
Nicola M Fenty
James M Hagberg
Stephen M Roth
David M Mosser
Min Qi Wang
Hanjoong Jo
Toshihiko Okazaki
Steven R Brant
Michael D Brown
University of Maryland, Baltimore · USJohns Hopkins University · USUniversity of Maryland, College Park · USEmory University · US

Funding

MODULATING HOST RESPONSES TO BACTERIAL PRODUCTSR01AI049383 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI MOSSER, DAVID M · 2001 to 2011
$3.1M
ACE GENOTYPE, BP, AND EXERCISE TRAINING IN HYPERTENSIVESR01AG017474 · NIA · UNIVERSITY OF MARYLAND COLLEGE PK CAMPUS · PI HAGBERG, JAMES M · 2000 to 2004
$2.1M
Crohn's Disease Gene Mapping of Chromosome 16R01DK058189 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BRANT, STEVEN R · 2001 to 2005
$1.9M
Transcriptional regulation by TEF-1 in cardiac myocytesR01HL071894 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI FARRANCE, IAIN K · 2004 to 2007
$1.2M
Genetic Epidemiology of Aging Skeletal MuscleK01AG022791 · NIA · UNIV OF MARYLAND, COLLEGE PARK · PI ROTH, STEPHEN M · 2003 to 2007
$545k
ENOS Genotype, BP, and Exercise in African AmericansK01AG019640 · NIA · UNIV OF MARYLAND, COLLEGE PARK · PI BROWN, MICHAEL DAVID · 2003 to 2007
$407k
NHLBI NIH HHS HL-071894NHLBI NIH HHS R01 HL071894NIAID NIH HHS R01 AI049383NIA NIH HHS AG-019640NIA NIH HHS AG-022791NIA NIH HHS AG-17474NIA NIH HHS K01 AG019640NIA NIH HHS K01 AG022791NIA NIH HHS L30 AG024705NIA NIH HHS R01 AG017474NIDDK NIH HHS DK-58189NIDDK NIH HHS R01 DK058189
6 · The paper itself

Abstract

In endothelial cells, NF-kappaB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-kappa light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism ((-94)NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage I hypertensive individuals before and after a 6-mo supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the (-94)NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity.

Indexed as

Exercise TherapyPolymorphism, GeneticPromoter Regions, GeneticAgedCells, CulturedEndothelium, VascularEnzyme InductionFemaleForearmGenetic Predisposition to DiseaseHomozygoteHumansHyperemiaHypertensionMaleMiddle AgedNF-kappa B p50 SubunitNFKB1 protein, humanNitric Oxide Synthase Type IIINOS3 protein, human

Identifiers

PMID17644577
PMCPMC2614625
OpenAlexW1976307356

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.