Evidence map›Paper›PMID 40955561›Full record

ArticleCirculation research2025

Circular RNA Cdr1as Modulates Macrophage-Mediated Cardiac Reparative Function.

Carolina Gonzalez, Maria Cimini, Vandana Mallaredy, Cindy Benedict, Darukeshwara Joladarashi, Charan Thej, Zhongjian Cheng, May Trungcao, Amit Kumar Rai, Venkata Naga Srikanth Garikipati and 1 more

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 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
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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

11 authors.

Carolina GonzalezAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Maria CiminiAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Vandana MallaredyAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-1891-9758
Cindy BenedictAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0001-8380-161X
Darukeshwara JoladarashiAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-9466-9228
Charan ThejAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0001-9844-9735
Zhongjian ChengAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
May TrungcaoAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Amit Kumar RaiAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Venkata Naga Srikanth GarikipatiAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0009-0006-7811-9302
Raj KishoreAging and Cardiovascular Discovery Center (C.G., M.C., V.M., C.B., D.J., C.T., Z.C., M.T., A.K.R., V.N.S.G., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-7667-2458

Funding

Small and large animal surgery, physiology and histologyP01HL134608 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI Walter J. Koch · 2017 to 2026
$21.0M
Targeting Pathways Involved in Cardiac Injury for Novel Repair StrategiesP01HL147841 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ELROD, JOHN WILLIAM · 2020 to 2024
$11.4M
Restoration of myocardial reparative function of diabetic progenitor cells by epigenetic modulationR01HL143892 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 2020 to 2023
$2.2M
MyomiR-499, Exosomes and Endothelial and Endothelial Progenitor Cells dysfunction in DiabetesR01HL169405 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI Raj Kishore · 2024 to 2026
$1.8M
The Role of circ-Cdr1as in monocyte/macrophage mediated cardiac injury and repair.F31HL162543 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI GONZALEZ, CAROLINA · 2022 to 2024
$94k
NHLBI NIH HHS F31 HL162543NHLBI NIH HHS P01 HL134608NHLBI NIH HHS P01 HL147841NHLBI NIH HHS R01 HL143892NHLBI NIH HHS R01 HL169405
6 · The paper itself

Abstract

backgroundMechanisms of macrophage switching from proinflammatory to anti-inflammatory phenotypes are not well understood. Circular RNAs, a new class of noncoding RNAs, are implicated in immune modulation. We recently identified circ-cdr1as as a regulator of macrophage phenotype in bone marrow-derived macrophages; however, its role in immunomodulation during cardiovascular injury remains unknown.

methodsCell-specific expression levels of circ-cdr1as were determined in the mouse hearts postmyocardial infarction. Circ-cdr1as was overexpressed in fluorescently labeled bone marrow-derived macrophages and injected into the ischemic myocardium immediately following myocardial infarction. The effect of AAV9 (adeno-associated virus-serotype 9)-mediated systemic delivery of circ-Cdr1as on postmyocardial infarction cardiac function and structure was determined. Downstream mechanisms were studied using gain and loss-of-function strategies.

resultsCardiac cell-specific expression analysis showed significant downregulation of circ-cdr1as only in macrophages and cardiomyocytes. Overexpression of circ-cdr1as in bone marrow-derived macrophages, injected into the ischemic myocardium, retained their anti-inflammatory phenotype and significantly improved left ventricular functions and reduced infarct size. Systemic delivery of AAV9-circ-cdr1as showed similar cardiac reparative activity. Mechanistically, circ-cdr1as directly binds and sponges microRNA-7 and increases the expression of target KLF4 (Kruppel-like factor 4). Loss and gain of function studies show that modulation of microRNA 7 and KLF recapitulates macrophage phenotypic changes.

conclusionsCirc-cdr1as plays a crucial role in regulating the anti-inflammatory phenotype of macrophages through modulation of microRNA 7 and its target gene KLF4. Therefore, circ-cdr1as holds potential as an anti-inflammatory regulator in tissue inflammation postcardiac injury.

Indexed as

MacrophagesMyocardial InfarctionRNA, CircularAnimalsCells, CulturedDisease Models, AnimalHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMicroRNAsMyocytes, CardiacVentricular Function, LeftKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMicroRNAsRNA, CircularimmunomodulationinflammationmicemicroRNAmyocardial infarction

Identifiers

PMID40955561
PMCPMC12536452

What Socratic 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 Socratic graph.