Evidence map›Paper›PMID 37097749›Full record

ArticleJCI insight2023

Impaired angiogenesis in diabetic critical limb ischemia is mediated by a miR-130b/INHBA signaling axis.

Henry S Cheng, Daniel Pérez-Cremades, Rulin Zhuang, Anurag Jamaiyar, Winona Wu, Jingshu Chen, Aspasia Tzani, Lauren Stone, Jorge Plutzky, Terence E Ryan and 5 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. MicroRNAs in diabetic macroangiopathy.Cardiovascular diabetology · 2024
    Review
  6. Article
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

15 authors at 4 institutions in 3 countries.

Henry S ChengDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Daniel Pérez-CremadesDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Rulin ZhuangDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Anurag JamaiyarDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Winona WuDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jingshu ChenDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Aspasia TzaniDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Lauren StoneDepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
Jorge PlutzkyDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Terence E RyanDepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
Philip P GoodneyHeart and Vascular Center, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Mark A CreagerHeart and Vascular Center, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Marc S SabatineDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Marc P BonacaCPC Clinical Research, University of Colorado, Denver, Colorado, USA.
Mark W FeinbergDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USUniversity of Florida · USDartmouth–Hitchcock Medical Center · USUniversity of Colorado Denver · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
MiR-181b, endothelial cells, and vascular inflammationR01HL115141 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FEINBERG, MARK W · 2012 to 2024
$6.8M
miR-615, AKT/eNOS signaling, and angiogenesisR01HL148207 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FEINBERG, MARK W · 2020 to 2023
$2.6M
LncRNA SNHG12, vascular senescence, and atherosclerosisR01HL148355 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FEINBERG, MARK W · 2020 to 2023
$2.5M
KLF10, CD4+ T cells, and transplant arteriopathyR01HL134849 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FEINBERG, MARK W · 2017 to 2020
$1.7M
LncRNA MAARS, macrophage apoptosis, and atherosclerosisR01HL153356 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FEINBERG, MARK W · 2020 to 2023
$1.7M
NHLBI NIH HHS R01 HL115141NHLBI NIH HHS R01 HL134849NHLBI NIH HHS R01 HL148207NHLBI NIH HHS R01 HL148355NHLBI NIH HHS R01 HL153356NIDDK NIH HHS P30 DK034854
6 · The paper itself

Abstract

Patients with peripheral artery disease (PAD) and diabetes compose a high-risk population for development of critical limb ischemia (CLI) and amputation, although the underlying mechanisms remain poorly understood. Comparison of dysregulated microRNAs from diabetic patients with PAD and diabetic mice with limb ischemia revealed the conserved microRNA, miR-130b-3p. In vitro angiogenic assays demonstrated that miR-130b rapidly promoted proliferation, migration, and sprouting in endothelial cells (ECs), whereas miR-130b inhibition exerted antiangiogenic effects. Local delivery of miR-130b mimics into ischemic muscles of diabetic mice (db/db) following femoral artery ligation (FAL) promoted revascularization by increasing angiogenesis and markedly improved limb necrosis and amputation. RNA-Seq and gene set enrichment analysis from miR-130b-overexpressing ECs revealed the BMP/TGF-β signaling pathway as one of the top dysregulated pathways. Accordingly, overlapping downregulated transcripts from RNA-Seq and miRNA prediction algorithms identified that miR-130b directly targeted and repressed the TGF-β superfamily member inhibin-β-A (INHBA). miR-130b overexpression or siRNA-mediated knockdown of INHBA induced IL-8 expression, a potent angiogenic chemokine. Lastly, ectopic delivery of silencer RNAs (siRNA) targeting Inhba in db/db ischemic muscles following FAL improved revascularization and limb necrosis, recapitulating the phenotype of miR-130b delivery. Taken together, a miR-130b/INHBA signaling axis may provide therapeutic targets for patients with PAD and diabetes at risk of developing CLI.

Indexed as

Diabetes Mellitus, ExperimentalMicroRNAsAnimalsChronic Limb-Threatening IschemiaEndothelial CellsHumansInhibin-beta SubunitsInhibinsIschemiaMiceNecrosisRNA, Small InterferingSignal TransductionTransforming Growth Factor betainhibin beta A subunitInhibin-beta SubunitsInhibinsMicroRNAsMIRN130 microRNA, mouseRNA, Small InterferingTransforming Growth Factor betaAngiogenesisEndothelial cellsMouse modelsNoncoding RNAsVascular Biology

Identifiers

PMID37097749
PMCPMC10322685
OpenAlexW4366983108

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.