Evidence map›Paper›PMID 22168264›Full record

ArticleAging cell2012

Superoxide-lowering therapy with TEMPOL reverses arterial dysfunction with aging in mice.

Bradley S Fleenor, Douglas R Seals, Melanie L Zigler, Amy L Sindler

Open access · bronzeAbstract read
In one paragraph

Article in Aging cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
7.4field-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

85 citing papers in PubMed, 131 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. The role of NO, HBasic research in cardiology · 2025
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  12. Article
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  14. Effects of regular exercise on vascular function with aging: Does sex matter?American journal of physiology. Heart and circulatory physiology · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Pyridoxamine treatment ameliorates large artery stiffening and cerebral artery endothelial dysfunction in old mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
  19. Article
  20. Review

25 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

4 authors at 1 institution in 1 country.

Bradley S FleenorDepartment of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. bradley.fleenor@colorado.edu
Douglas R Seals
Melanie L Zigler
Amy L Sindler
University of Colorado Boulder · US

Funding

University of Colorado Aging Training GrantT32AG000279 · NIA · UNIVERSITY OF COLORADO DENVER · PI Kerrie Moreau · 2001 to 2026
$10.1M
POSTGRADUATE TRAINING IN CARDIOVASCULAR RESEARCHT32HL007822 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BUTTRICK, PETER N., LEINWAND, LESLIE ANNE · 1996 to 2023
$6.2M
SODIUM RESTRICTION &ARTERIAL COMPLIANCE IN OLDER HUMANSR01AG013038 · NIA · UNIVERSITY OF COLORADO AT BOULDER · PI SEALS, DOUGLAS R · 1996 to 2018
$4.0M
Human Aging, Exercise &FMD: Translational PhysiologyR37AG013038 · NIA · UNIVERSITY OF COLORADO AT BOULDER · PI SEALS, DOUGLAS R · 2004 to 2013
$3.0M
Aging and Arterial Dysfunction with a Western Diet: Exercise and AMPKR01HL107120 · NHLBI · UNIVERSITY OF COLORADO · PI SEALS, DOUGLAS R · 2011 to 2014
$1.6M
NHLBI NIH HHS HL007822NHLBI NIH HHS HL107120NHLBI NIH HHS R01 HL107120NHLBI NIH HHS T32 HL007822NIA NIH HHS AG000279NIA NIH HHS AG013038NIA NIH HHS R01 AG013038NIA NIH HHS R37 AG013038NIA NIH HHS T32 AG000279
6 · The paper itself

Abstract

To test the hypothesis that the antioxidant enzyme superoxide dismutase (SOD) mimetic TEMPOL improves arterial aging, young (Y, 4-6 months) and old (O, 26-28 months) male C57BL6 mice received regular or TEMPOL-supplemented (1mM) drinking water for 3 weeks (n = 8 per group). Aortic superoxide was 65% greater in O (P < 0.05 vs. Y), which was normalized by TEMPOL. O had large elastic artery stiffening, as indicated by greater aortic pulse wave velocity (aPWV, 508 ± 22 vs. 418 ± 22 AU), which was associated with increased adventitial collagen I expression (P < 0.05 vs. Y). TEMPOL reversed the age-associated increases in aPWV (434 ± 21 AU) and collagen in vivo, and SOD reversed the increases in collagen I in adventitial fibroblasts from older rats in vitro. Isolated carotid arteries of O had impaired endothelial function as indicated by reduced acetylcholine-stimulated endothelium-dependent dilation (EDD) (75.6 ± 3.2 vs. 94.5 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (L-NAME) associated with decreased endothelial NO synthase (eNOS) expression (P < 0.05 vs. Y). TEMPOL restored EDD (94.5 ± 1.4%), NO bioavailability and eNOS in O. Nitrotyrosine and expression of NADPH oxidase were ~100-200% greater, and MnSOD was ~75% lower in O (P < 0.05 vs. Y). TEMPOL normalized nitrotyrosine and NADPH oxidase in O, without affecting MnSOD. Aortic pro-inflammatory cytokines were greater in O (P < 0.05 vs. Y) and normalized by TEMPOL. Short-term treatment of excessive superoxide with TEMPOL ameliorates large elastic artery stiffening and endothelial dysfunction with aging, and this is associated with normalization of arterial collagen I, eNOS, oxidative stress, and inflammation.

Indexed as

AgingAnimalsAntioxidantsCollagenCyclic N-OxidesMaleMiceNADPH OxidasesOxidative StressRatsSpin LabelsSuperoxidesVascular DiseasesAntioxidantsCollagenCyclic N-OxidesNADPH OxidasesSpin LabelsSuperoxidestempol

Identifiers

PMID22168264
PMCPMC3409251
OpenAlexW1946826431

What OpenQuestion holds

Textmetadata
LicenceTDM
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.