Evidence map›Paper›PMID 34403365›Full record

ArticleJCI insight2021

Autophagy-mitophagy induction attenuates cardiovascular inflammation in a murine model of Kawasaki disease vasculitis.

Stefanie Marek-Iannucci, Asli B Ozdemir, Debbie Moreira, Angela C Gomez, Malcolm Lane, Rebecca A Porritt, Youngho Lee, Kenichi Shimada, Masanori Abe, Aleksandr Stotland and 10 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
16.3field-weighted citation impact, top 1% 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

36 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
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  9. Impact of breastfeeding andFrontiers in immunology · 2026
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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

20 authors at 4 institutions in 1 country.

Stefanie Marek-IannucciGraduate School of Biomedical Sciences.
Asli B OzdemirDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Debbie MoreiraDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Angela C GomezDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Malcolm LaneDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Rebecca A PorrittDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Youngho LeeDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Kenichi ShimadaDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Masanori AbeDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Aleksandr StotlandAdvanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
David ZemmourDepartment of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Sarah ParkerAdvanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Elsa Sanchez-LopezLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, UCSD, San Diego, California, USA.
Jennifer Van EykAdvanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Roberta A GottliebSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Michael C FishbeinDepartment of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Michael KarinLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, UCSD, San Diego, California, USA.
Timothy R CrotherDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Magali Noval RivasDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Moshe ArditiDepartment of Pediatrics, Division of Infectious Diseases and Immunology.
Cedars-Sinai Medical Center · USUniversity of California San Diego · USBrigham and Women's Hospital · USUniversity of California, Los Angeles · US

Funding

Role of IL-1 in Bacterial ligand-induced vasculitis and myocarditisR01AI072726 · NIAID · CEDARS-SINAI MEDICAL CENTER · PI ARDITI, MOSHE · 2008 to 2020
$4.5M
Role of intestinal microbiome and gut permeability in the development of Kawasaki Disease vasculitisR01HL139766 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI Magali Noval Rivas · 2018 to 2026
$3.4M
NHLBI NIH HHS R01 HL139766NIAID NIH HHS R01 AI072726
6 · The paper itself

Abstract

Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Murine and human data suggest that the NLRP3-IL-1β pathway is the main driver of KD pathophysiology. NLRP3 can be activated during defective autophagy/mitophagy. We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to examine the role of autophagy/mitophagy on cardiovascular lesion development. LCWE-injected mice had impaired autophagy/mitophagy and increased levels of ROS in cardiovascular lesions, together with increased systemic 8-OHdG release. Enhanced autophagic flux significantly reduced cardiovascular lesions in LCWE-injected mice, whereas autophagy blockade increased inflammation. Vascular smooth muscle cell-specific deletion of Atg16l1 and global Parkin-/- significantly increased disease formation, supporting the importance of autophagy/mitophagy in this model. Ogg1-/- mice had significantly increased lesions with increased NLRP3 activity, whereas treatment with MitoQ reduced vascular tissue inflammation, ROS production, and systemic 8-OHdG release. Treatment with MN58b or Metformin (increasing AMPK and reducing ROS) resulted in decreased cardiovascular lesions. Our results demonstrate that impaired autophagy/mitophagy and ROS-dependent damage exacerbate the development of murine KD vasculitis. This pathway can be efficiently targeted to reduce disease severity. These findings enhance our understanding of KD pathogenesis and identify potentially novel therapeutic avenues for KD treatment.

Indexed as

AutophagyMitophagy8-Hydroxy-2'-DeoxyguanosineAnimalsAutophagy-Related ProteinsButanesCell ExtractsCell WallCoronary VesselsDisease Models, AnimalDNA GlycosylasesHypoglycemic AgentsLacticaseibacillus caseiMaleMetforminMice1,4-(4-4'-Bis-((4-(dimethylamine)pyridinium-1-yl) methyl)diphenyl)butane dibromide8-Hydroxy-2'-DeoxyguanosineAtg16l1 protein, mouseAutophagy-Related ProteinsButanesCell ExtractsDNA GlycosylasesHypoglycemic AgentsMetforminmitoquinoneNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseOgg1 protein, mouseOrganophosphorus Compoundsparkin proteinPyridinium CompoundsReactive Oxygen SpeciesUbiquinoneUbiquitin-Protein LigasesInflammationInnate immunityVascular BiologyVasculitis

Identifiers

PMID34403365
PMCPMC8492304
OpenAlexW3193605806

What Socratic holds

Textmetadata
LicenceCC BY
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.