Evidence map›Paper›PMID 39895524›Full record

ArticleJournal of the American Heart Association2025

Vascular Contractility Relies on Integrity of Progranulin Pathway: Insights Into Mitochondrial Function.

Shubhnita Singh, Ariane Bruder, Rafael M Costa, Juliano V Alves, Sivakama Bharathi, Eric S Goetzman, Thiago Bruder-Nascimento

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2025. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Progranulin deficiency induces premature vascular senescence and dysfunction.American journal of physiology. Heart and circulatory physiology · 2026
    Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Shubhnita SinghDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.ORCID 0000-0002-1835-2317
Ariane BruderDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.ORCID 0009-0005-7067-4048
Rafael M CostaDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.ORCID 0000-0002-5174-5710
Juliano V AlvesDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.ORCID 0000-0002-6555-5547
Sivakama BharathiDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.
Eric S GoetzmanDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.ORCID 0000-0001-9476-309X
Thiago Bruder-NascimentoDepartment of Pediatrics at UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA.ORCID 0000-0001-5671-318X

Funding

Molecular mechanisms of progranulin as a regulator of endothelial biology and blood pressure controlR01HL169202 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI Thiago Bruder · 2024 to 2026
$1.5M
Leptin, a therapeutic avenue for the treatment of vascular disease, focus on congenital and antiretroviral therapy-associated lipodystrophiesR00HL140139 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BRUDER, THIAGO · 2019 to 2021
$733k
NHLBI NIH HHS R00 HL140139NHLBI NIH HHS R01 HL169202
6 · The paper itself

Abstract

backgroundThe complex interplay between vascular contractility and mitochondrial function is central to cardiovascular disease. The progranulin gene ( METHODS AND

resultsWe used aortae from male and female C57BL6/J wild-type (PGRN+/+) and B6(Cg)-Grntm1.1Aidi/J (PGRN-/-) mice. Our results showed suppression of contractile activity in PGRN-/-, followed by reduced α-smooth muscle actin expression. Mechanistically, PGRN deficiency suppressed mitochondrial respiration, induced mitochondrial fission, and disturbed autophagy process and redox signaling, while restoration of PGRN levels in aortae from PGRN-/- mice via lentivirus delivery ameliorated contractility and boosted mitochondria activity. In addition, in vivo treatment with mitochondrial fission inhibitor restored mitochondrial quality and vascular contractility, while vascular smooth muscle cells overexpressing PGRN displayed higher lysosome biogenesis, accelerated mitophagy flux, and mitochondrial respiration accompanied by vascular hypercontractility. Finally, angiotensin II failed to induce vascular contractility in PGRN-/-, suggesting a key role of PGRN to maintain the vascular tone.

conclusionsOur findings suggest that PGRN preserves the vascular contractility via regulating mitophagy flux, mitochondrial activity and dynamics, and redox signaling. Therefore, loss of PGRN function appears as a pivotal risk factor in cardiovascular disease.

Indexed as

AortaMitochondriaMitochondria, MuscleMuscle, Smooth, VascularMyocytes, Smooth MuscleProgranulinsVasoconstrictionAnimalsAutophagyFemaleMaleMiceMice, Inbred C57BLMice, KnockoutMitochondrial DynamicsMitophagyGrn protein, mouseProgranulinsprogranulinvascular contractilityvasculature

Identifiers

PMID39895524
PMCPMC12074767

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.