Evidence map›Paper›PMID 36098045›Full record

ArticleCirculation research2022

Extracellular Vesicles Regulate Sympatho-Excitation by Nrf2 in Heart Failure.

Changhai Tian, Lie Gao, Tara L Rudebush, Li Yu, Irving H Zucker

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Protection byPharmaceuticals (Basel, Switzerland) · 2026
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
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

5 authors at 2 institutions in 1 country.

Changhai TianDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington' KY. (C.T.).
Lie GaoDepartment of Anesthesiology (L.G.), University of Nebraska Medical Center, Omaha, NE.ORCID 0000-0002-7880-7213
Tara L RudebushDepartment of Cellular and Integrative Physiology (T.L.R., L.Y., I.H.Z.), University of Nebraska Medical Center, Omaha, NE.
Li YuDepartment of Cellular and Integrative Physiology (T.L.R., L.Y., I.H.Z.), University of Nebraska Medical Center, Omaha, NE.
Irving H ZuckerDepartment of Cellular and Integrative Physiology (T.L.R., L.Y., I.H.Z.), University of Nebraska Medical Center, Omaha, NE.ORCID 0000-0003-3636-7720
University of Nebraska Medical Center · USUniversity of Kentucky · US

Funding

The Role of Excitatory Input into the PVN on Increased Sympathetic Drive in HeartP01HL062222 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI CORNISH, KURTIS G · 1999 to 2019
$32.2M
Nrf2 regulation of oxidative stress in heart failure and extra vesicular communicationR01HL153176 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI TIAN, CHANGHAI, ZUCKER, IRVING H · 2021 to 2024
$2.6M
NHLBI NIH HHS P01 HL062222NHLBI NIH HHS R01 HL153176
6 · The paper itself

Abstract

backgroundChronic heart failure (CHF) is associated with redox imbalance. Downregulation of Nrf2 (nuclear factor [erythroid-derived 2]-like 2) plays important roles in disrupting myocardial redox homeostasis and mediating sympathetic nerve activity in the setting of CHF. However, it is unclear if circulating extracellular vesicles (EVs) elicit sympathetic excitation in CHF by disrupting central redox homeostasis. We tested the hypothesis that cardiac-derived EVs circulate to the presympathetic rostral ventrolateral medulla and contribute to oxidative stress and sympathetic excitation via EV-enriched microRNA-mediated Nrf2 downregulation.

methodsData were collected on rats with CHF post-myocardial infarction (MI) and on human subjects with ischemic CHF. EVs were isolated from tissue and plasma, and we determined the miRNAs cargo that related to targeting Nrf2 translation. We tracked the distribution of cardiac-derived EVs using in vitro labeled circulating EVs and cardiac-specific membrane GFP

resultsNrf2 downregulation in CHF rats was associated with an upregulation of Nrf2-targeting miRNAs, which were abundant in cardiac-derived and circulating EVs from rats and humans. EVs isolated from the brain of CHF rats were also enriched with Nrf2-targeting miRNAs and cardiac-specific miRNAs. Cardiac-derived EVs were taken up by neurons in the rostral ventrolateral medulla. The administration of cardiac-derived and circulating EVs from CHF rats into the rostral ventrolateral medulla of normal rats evoked an increase in renal sympathetic nerve activity and plasma norepinephrine compared with Sham-operated rats, which were attenuated by exogenously preloading CHF-EVs with antagomirs to Nrf2-targeting miRNAs.

conclusionsCardiac microRNA-enriched EVs from animals with CHF can mediate crosstalk between the heart and the brain in the regulation of sympathetic outflow by targeting the Nrf2/antioxidant signaling pathway. This new endocrine signaling pathway regulating sympathetic outflow in CHF may be exploited for novel therapeutics.

Indexed as

Extracellular VesiclesHeart FailureMicroRNAsAnimalsAntagomirsAntioxidantsHumansMiceNF-E2-Related Factor 2NorepinephrineRatsSympathetic Nervous SystemAntagomirsAntioxidantsMicroRNAsNF-E2-Related Factor 2Norepinephrineantioxidantextracellular vesiclesheart failureoxidative stresssympathetic nervous system

Identifiers

PMID36098045
PMCPMC9529870
OpenAlexW4295413956

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.