Evidence map›Paper›PMID 35166002›Full record

ArticleAging cell2022

Fibronectin type III domain-containing 5 improves aging-related cardiac dysfunction in mice.

Can Hu, Xin Zhang, Min Hu, Teng Teng, Yu-Pei Yuan, Peng Song, Chun-Yan Kong, Si-Chi Xu, Zhen-Guo Ma, Qi-Zhu Tang

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
9.2field-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

42 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Cellular and molecular mechanisms underlying cardiovascular aging.Cellular & molecular biology letters · 2025
    Review
  6. Inhibition of AMPKα Pathway by Podocyte GOLM1 Exacerbates Diabetic Nephrology in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. Article
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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

10 authors at 1 institution in 1 country.

Can HuDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Xin ZhangDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Min HuDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Teng TengDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Yu-Pei YuanDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Peng SongDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Chun-Yan KongDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Si-Chi XuDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Zhen-Guo MaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Qi-Zhu TangDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.ORCID 0000-0003-2210-3169
Wuhan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aging is an important risk factor for cardiovascular diseases, and aging-related cardiac dysfunction serves as a major determinant of morbidity and mortality in elderly populations. Our previous study has identified fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, as the cardioprotectant against doxorubicin-induced cardiomyopathy. Herein, aging or matched young mice were overexpressed with FNDC5 by adeno-associated virus serotype 9 (AAV9) vectors, or subcutaneously infused with irisin to uncover the role of FNDC5 in aging-related cardiac dysfunction. To verify the involvement of nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) and AMP-activated protein kinase α (AMPKα), Nlrp3 or Ampkα2 global knockout mice were used. Besides, young mice were injected with AAV9-FNDC5 and maintained for 12 months to determine the preventive effect of FNDC5. Moreover, neonatal rat cardiomyocytes were stimulated with tumor necrosis factor-α (TNF-α) to examine the role of FNDC5 in vitro. We found that FNDC5 was downregulated in aging hearts. Cardiac-specific overexpression of FNDC5 or irisin infusion significantly suppressed NLRP3 inflammasome and cardiac inflammation, thereby attenuating aging-related cardiac remodeling and dysfunction. In addition, irisin treatment also inhibited cellular senescence in TNF-α-stimulated cardiomyocytes in vitro. Mechanistically, FNDC5 activated AMPKα through blocking the lysosomal degradation of glucagon-like peptide-1 receptor. More importantly, FNDC5 gene transfer in early life could delay the onset of cardiac dysfunction during aging process. We prove that FNDC5 improves aging-related cardiac dysfunction by activating AMPKα, and it might be a promising therapeutic target to support cardiovascular health in elderly populations.

Indexed as

Fibronectin Type III DomainHeart DiseasesAgingAMP-Activated Protein KinasesAnimalsFibronectinsMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinRatsTumor Necrosis Factor-alphaAMP-Activated Protein KinasesFibronectinsFNDC5 protein, mouseFNDC5 protein, ratNLR Family, Pyrin Domain-Containing 3 ProteinTumor Necrosis Factor-alphaaging-related cardiac dysfunctionAMPKαFNDC5inflammation

Identifiers

PMID35166002
PMCPMC8920441
OpenAlexW4213106105

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.