Evidence map›Paper›PMID 27940350›Full record

ReviewFree radical biology & medicine2017

Responses to reductive stress in the cardiovascular system.

Diane E Handy, Joseph Loscalzo

Open access · greenAbstract readReview
In one paragraph

Review in Free radical biology & medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
7.7field-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

72 citing papers in PubMed, 146 citations in OpenAlex.

  1. Review
  2. Review
  3. Reductive stress in cancer immunology and targeted therapy.Acta biochimica et biophysica Sinica · 2026
    Review
  4. Review
  5. Review
  6. Redox Control in Platelet Activity and Therapy.Antioxidants (Basel, Switzerland) · 2025
    Review
  7. Article
  8. Article
  9. Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Metabolic Responses to Redox Stress in Vascular Cells.Antioxidants & redox signaling · 2024
    Review
  18. Article
  19. Article
  20. Article

12 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

2 authors at 2 institutions in 1 country.

Diane E HandyDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, USA.
Joseph LoscalzoDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, USA. Electronic address: jloscalzo@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USHarvard University · US

Funding

Tissue AnalysesP01HL048743 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLADYSHEV, VADIM N. · 1992 to 2014
$26.3M
TRANSLATIONAL PHARMACOLOGY COREP50GM107618 · NIGMS · HARVARD MEDICAL SCHOOL · PI MALISZEWSKI, LAURA ELIZABETH · 2014 to 2018
$10.8M
Center for Integrated Approaches to Undiagnosed DiseasesU01HG007690 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2014 to 2022
$10.4M
GPx-3 and Peroxide Flux in the Endothelial CellR37HL061795 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2007 to 2016
$4.3M
NHGRI NIH HHS U01 HG007690NHLBI NIH HHS P01 HL048743NHLBI NIH HHS R37 HL061795NIGMS NIH HHS P50 GM107618
6 · The paper itself

Abstract

There is a growing appreciation that reductive stress represents a disturbance in the redox state that is harmful to biological systems. On a cellular level, the presence of increased reducing equivalents and the lack of beneficial fluxes of reactive oxygen species can prevent growth factor-mediated signaling, promote mitochondrial dysfunction, increase apoptosis, and decrease cell survival. In this review, we highlight the importance of redox balance in maintaining cardiovascular homeostasis and consider the tenuous balance between oxidative and reductive stress. We explain the role of reductive stress in models of protein aggregation-induced cardiomyopathies, such as those caused by mutations in αB-crystallin. In addition, we discuss the role of NADPH oxidases in models of heart failure and ischemia-reperfusion to illustrate how oxidants may mediate the adaptive responses to injury. NADPH oxidase 4, a hydrogen peroxide generator, also has a major role in promoting vascular homeostasis through its regulation of vascular tone, angiogenic responses, and effects on atherogenesis. In contrast, the lack of antioxidant enzymes that reduce hydrogen peroxide, such as glutathione peroxidase 1, promotes vascular remodeling and is deleterious to endothelial function. Thus, we consider the role of oxidants as necessary signals to promote adaptive responses, such as the activation of Nrf2 and eNOS, and the stabilization of Hif1. In addition, we discuss the adaptive metabolic reprogramming in hypoxia that lead to a reductive state, and the subsequent cellular redistribution of reducing equivalents from NADH to other metabolites. Finally, we discuss the paradoxical ability of excess reducing equivalents to stimulate oxidative stress and promote injury.

Indexed as

alpha-Crystallin B ChainAnimalsCardiomyopathiesCardiovascular SystemCell SurvivalGene Expression RegulationHeart FailureHomeostasisHumansMyocardial Reperfusion InjuryNF-E2-Related Factor 2Nitric Oxide Synthase Type IIIOxidation-ReductionOxidative StressReactive Oxygen SpeciesSignal Transductionalpha-Crystallin B ChainNFE2L2 protein, humanNF-E2-Related Factor 2Nitric Oxide Synthase Type IIINOS3 protein, humanReactive Oxygen SpeciesAntioxidantCardiovascularHypoxiaNox4Nrf2Oxidative stressRedoxReductive stressαΒ-crystallin

Identifiers

PMID27940350
PMCPMC5462861
OpenAlexW2560693613

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.