Evidence map›Paper›PMID 40960950›Full record

ArticleCirculation research2025

Septin4 Regulates Cardiac Fibrosis After Pressure Overload.

Doğacan Yücel, Natalia Ferreira de Araujo, Fernando Souza-Neto, Calvin Smith, Wei-Han Lin, Andrea A Torniainen, Mikayla L Hall, DeWayne Townsend, Brenda M Ogle, Jop H van Berlo

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Protective Effects ofFood science & nutrition · 2026
    Article
  2. 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

10 authors.

Doğacan Yücel *Department of Integrative Biology and Physiology (D.Y., D.W.T., J.H.v.B.), University of Minnesota, Minneapolis.ORCID 0009-0005-0471-7388
Natalia Ferreira de Araujo *Department of Medicine, Lillehei Heart Institute (D.Y., N.F.A., F.S.-N., C.S., A.A.T., J.H.v.B.), University of Minnesota, Minneapolis.
Fernando Souza-NetoDepartment of Medicine, Lillehei Heart Institute (D.Y., N.F.A., F.S.-N., C.S., A.A.T., J.H.v.B.), University of Minnesota, Minneapolis.
Calvin SmithDepartment of Medicine, Lillehei Heart Institute (D.Y., N.F.A., F.S.-N., C.S., A.A.T., J.H.v.B.), University of Minnesota, Minneapolis.
Wei-Han LinDepartment of Biomedical Engineering (W.-H.L., M.L.H., B.M.O.), University of Minnesota, Minneapolis.ORCID 0009-0006-1174-4736
Andrea A TorniainenDepartment of Medicine, Lillehei Heart Institute (D.Y., N.F.A., F.S.-N., C.S., A.A.T., J.H.v.B.), University of Minnesota, Minneapolis.
Mikayla L HallDepartment of Biomedical Engineering (W.-H.L., M.L.H., B.M.O.), University of Minnesota, Minneapolis.
DeWayne TownsendDepartment of Integrative Biology and Physiology (D.Y., D.W.T., J.H.v.B.), University of Minnesota, Minneapolis.ORCID 0000-0002-0246-9692
Brenda M OgleDepartment of Biomedical Engineering (W.-H.L., M.L.H., B.M.O.), University of Minnesota, Minneapolis.
Jop H van BerloDepartment of Integrative Biology and Physiology (D.Y., D.W.T., J.H.v.B.), University of Minnesota, Minneapolis.ORCID 0000-0001-9229-4429

Funding

Computational and Experimental Modeling of Cardiomyocyte ProliferationR01HL160665 · NHLBI · UNIVERSITY OF VIRGINIA · 2022 to 2025
$2.8M
NHLBI NIH HHS R01 HL160665
6 · The paper itself

Abstract

backgroundIn response to cardiac injury the mammalian heart undergoes ventricular remodeling to maintain cardiac function. These changes are initially considered compensatory, but eventually lead to increased cardiomyocyte apoptosis, reduced cardiac function and fibrosis which are important contributors to the development of heart failure. The small GTPase Sept4 (Septin4) has previously been implicated in the regulation of regeneration and apoptosis in several organs. However, the role of Sept4 in regulating the response of the heart to stress is unknown.

methodsTen-week-old wild-type (WT) and Sept4 knockout mice were subjected to transverse aortic constriction to induce cardiac injury. Genotype-dependent differences were investigated at baseline and at 1- and 4-week postinjury time points. To definitively establish the fibroblast-specific cardioprotective effects of Sept4, we generated a fibroblast-specific Sept4 conditional knockout model.

resultsUnder homeostatic conditions Sept4 knockout mice showed normal cardiac function comparable with WT controls. In response to transverse aortic constriction, WT mice developed reduced cardiac function and heart failure, accompanied by an increase in cardiomyocyte apoptosis. In contrast, knockout mice were protected against injury with maintenance of normal cardiac function and reduced levels of cardiomyocyte apoptosis. Both at baseline and after transverse aortic constriction, knockout hearts exhibited decreased levels of cardiac extracellular matrix deposition and fibrosis compared with WT controls. In support of these data, the level of myofibroblast activation was lower after injury in knockout mice. Furthermore, the knockout group showed higher levels of cardiac compliance and improved diastolic function compared with WT controls. Mechanistically, we identified reduced fibrosis development due to alterations in calcineurin-dependent signaling in fibroblasts. These results were further verified in fibroblast-specific conditional Sept4 knockout mice subjected to cardiac pressure overload.

conclusionsWe identified Sept4 as an important regulator of extracellular matrix remodeling in the heart. Sept4 controls the conversion of fibroblast to myofibroblast through calcineurin-dependent mechanisms.

Indexed as

Heart FailureMyocardiumSeptinsAnimalsApoptosisDisease Models, AnimalFibroblastsFibrosisMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacVentricular RemodelingSept4 protein, mouseSeptinscardiovascular diseaseconstrictionfibrosisheart failuremyofibroblast

Identifiers

PMID40960950
PMCPMC12466173

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.