Evidence map›Paper›PMID 26054376›Full record

ArticleAntioxidants & redox signaling2015

NOX4 NADPH Oxidase-Dependent Mitochondrial Oxidative Stress in Aging-Associated Cardiovascular Disease.

Aleksandr E Vendrov, Kimberly C Vendrov, Alberto Smith, Jinling Yuan, Arihiro Sumida, Jacques Robidoux, Marschall S Runge, Nageswara R Madamanchi

Open access · greenAbstract read
In one paragraph

Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

120 citing papers in PubMed, 221 citations in OpenAlex.

  1. Article
  2. Review
  3. Aging-AssociatedJournal of the American Heart Association · 2026
    Article
  4. mBio · 2026
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  18. Klotho relieves HInternational ophthalmology · 2024
    Article
  19. Article
  20. Article

60 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Aleksandr E Vendrov1 Department of Medicine, McAllister Heart Institute, University of North Carolina , Chapel Hill, North Carolina.
Kimberly C Vendrov2 Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina.
Alberto Smith3 Cardiovascular Division, Academic Department of Surgery, National Institute for Health Research Biomedical Research Center at Guy's and St Thomas' National Health Service Foundation Trust , King's College London British Heart Foundation Centre of Excellence, London, United Kingdom .
Jinling Yuan1 Department of Medicine, McAllister Heart Institute, University of North Carolina , Chapel Hill, North Carolina.
Arihiro Sumida1 Department of Medicine, McAllister Heart Institute, University of North Carolina , Chapel Hill, North Carolina.
Jacques Robidoux4 Department of Pharmacology and Toxicology, The East Carolina Diabetes and Obesity Institute, East Carolina University , Greenville, North Carolina.
Marschall S Runge1 Department of Medicine, McAllister Heart Institute, University of North Carolina , Chapel Hill, North Carolina.
Nageswara R Madamanchi1 Department of Medicine, McAllister Heart Institute, University of North Carolina , Chapel Hill, North Carolina.
University of North Carolina at Chapel Hill · US

Funding

OXIDATIVE STRESS AND VASCULAR AGINGP01AG024282 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CLEMMONS, DAVID ROBERT · 2004 to 2008
$7.4M
Molecular Characterization of NoxA1 in VSMC NADPH Oxidase ActivationR01HL111664 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUNGE, MARSCHALL S. · 2012 to 2015
$1.5M
NCATS NIH HHS TR000083NHLBI NIH HHS HL111664NHLBI NIH HHS R01 HL111664NIA NIH HHS AG024282
6 · The paper itself

Abstract

aimsIncreased oxidative stress and vascular inflammation are implicated in increased cardiovascular disease (CVD) incidence with age. We and others demonstrated that NOX1/2 NADPH oxidase inhibition, by genetic deletion of p47phox, in Apoe(-/-) mice decreases vascular reactive oxygen species (ROS) generation and atherosclerosis in young age. The present study examined whether NOX1/2 NADPH oxidases are also pivotal to aging-associated CVD.

resultsBoth aged (16 months) Apoe(-/-) and Apoe(-/-)/p47phox(-/-) mice had increased atherosclerotic lesion area, aortic stiffness, and systolic dysfunction compared with young (4 months) cohorts. Cellular and mitochondrial ROS (mtROS) levels were significantly higher in aortic wall and vascular smooth muscle cells (VSMCs) from aged wild-type and p47phox(-/-) mice. VSMCs from aged mice had increased mitochondrial protein oxidation and dysfunction and increased vascular cell adhesion molecule 1 expression, which was abrogated with (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) treatment. NOX4 expression was increased in the vasculature and mitochondria of aged mice and its suppression with shRNA in VSMCs from aged mice decreased mtROS levels and improved function. Increased mtROS levels were associated with enhanced mitochondrial NOX4 expression in aortic VSMCs from aged subjects, and NOX4 expression levels in arterial wall correlated with age and atherosclerotic severity. Aged Apoe(-/-) mice treated with MitoTEMPO and 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione had decreased vascular ROS levels and atherosclerosis and preserved vascular and cardiac function. INNOVATION AND

conclusionThese data suggest that NOX4, but not NOX1/2, and mitochondrial oxidative stress are mediators of CVD in aging under hyperlipidemic conditions. Regulating NOX4 activity/expression and using mitochondrial antioxidants are potential approaches to reducing aging-associated CVD.

Indexed as

AgingAnimalsApolipoproteins ECardiovascular DiseasesCells, CulturedDisease Models, AnimalHumansMiceMitochondriaMuscle, Smooth, VascularMyocytes, Smooth MuscleNADPH Oxidase 4NADPH OxidasesOxidative StressApolipoproteins ENADPH Oxidase 4NADPH Oxidasesneutrophil cytosolic factor 1NOX4 protein, humanNox4 protein, mouse

Identifiers

PMID26054376
PMCPMC4692134
OpenAlexW1535736016

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.