Evidence map›Paper›PMID 42449490›Full record

ArticleActa physiologica (Oxford, England)2026

P2X7-NEK7-NLRP3 Axis Drives Cardiac Inflammation and Fibrosis in Isoproterenol-Induced Cardiac Remodeling in Mice.

Aline Cristina Parletta, Gabriela Cavazza Cerri, Marina Fevereiro, Karine Panico, Claudia Ribeiro Borba Gasparini, Denival Nascimento Vieira-Junior, Amanda de Almeida Silva, Nathalia Senger, Gabriela Placoná Diniz, Patrícia Castelucci and 2 more

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Article in Acta physiologica (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Aline Cristina ParlettaDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0003-4316-0218
Gabriela Cavazza CerriDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-1975-7420
Marina FevereiroDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-9858-3106
Karine PanicoDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0003-3783-3439
Claudia Ribeiro Borba GaspariniDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Denival Nascimento Vieira-JuniorDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Amanda de Almeida SilvaDepartment of Cardiopneumology, Heart Institute, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0009-0007-3226-8107
Nathalia SengerDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-9410-1050
Gabriela Placoná DinizDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0003-1278-4431
Patrícia CastelucciDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-7475-5962
Maria Cláudia Costa IrigoyenDepartment of Cardiopneumology, Heart Institute, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
Maria Luiza Morais Barreto-ChavesDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0001-5514-7921

Funding

Conselho Nacional de Desenvolvimento Científico e TecnológicoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior 001Fundação de Amparo à Pesquisa do Estado de São Paulo 2019/17031-2Fundação de Amparo à Pesquisa do Estado de São Paulo 2021/06151-7Fundação de Amparo à Pesquisa do Estado de São Paulo 2022/00086-1
6 · The paper itself

Abstract

aimCardiac remodeling (CR) is a critical risk factor for the development and progression of cardiovascular diseases. CR is accompanied by activation of the innate immune response, with NLRP3 inflammasome emerging as a key player in morphological and functional changes. However, the mechanisms underlying NLRP3 inflammasome assembly and activation in the heart upon beta-adrenergic overactivation remain poorly understood. This study aims to investigate the temporal profile of NLRP3 inflammasome activation and its upstream signaling P2X7-NEK7 in isoproterenol (ISO)-induced CR.

methodsWild-type (WT), NLRP3 knockout (NLRP3-KO), and P2X7-KO male mice were treated with ISO (60 mg/kg) for 1 h, 12 h, 24 h, or 14 days. Cardiac function was assessed by echocardiography and plethysmography. Cardiac hypertrophy and fibrosis were evaluated by histology. Fibrosis markers and cytokines gene expression were analyzed by quantitative PCR. Protein expression was evaluated by Western Blotting. Inflammasome assembly was confirmed by ASC speck immunofluorescence.

resultsWT mice showed a rapid activation of NLRP3 inflammasome in the heart up to 12 h from ISO administration, evidenced by increased NLRP3, ASC speck, Caspase-1, and IL-1β. ISO treatment for 12 h also increased P2X7 and NEK7. NLRP3-KO mice were protected from ISO-induced fibrosis and impairment of LV relaxation as well as the Caspase-1 activation and cytokines production. NEK7, NLRP3 activation, and fibrosis were prevented in P2X7-KO. NLRP3 deletion did not affect ISO-induced cardiac hypertrophy.

conclusionThese findings suggest that the NLRP3 inflammasome is activated by the P2X7-NEK7 pathway in the early stage of beta-adrenergic insult, driving ISO-induced cardiac fibrosis and inflammation.

Indexed as

IsoproterenolNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, Purinergic P2X7Ventricular RemodelingAnimalsCardiomegalyFibrosisInflammasomesInflammationMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumSignal TransductionInflammasomesIsoproterenolNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseP2rx7 protein, mouseReceptors, Purinergic P2X7cardiac dysfunctioncardiac hypertrophycardiac remodelingfibrosisinflammasomesinflammation

Identifiers

PMID42449490
PMCPMC13369798

What Socratic holds

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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 Socratic graph.