Evidence map›Paper›PMID 32641037›Full record

ArticleMolecular medicine (Cambridge, Mass.)2020

Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine.

Ulka Sachdev, Ricardo Ferrari, Xiangdong Cui, Abish Pius, Amrita Sahu, Michael Reynolds, Hong Liao, Ping Sun, Sunita Shinde, Fabrisia Ambrosio and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Regulation, Activation and Function of Caspase-11 during Health and Disease.International journal of molecular sciences · 2021
    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

13 authors at 3 institutions in 2 countries.

Ulka SachdevDivision of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA. Sachdevu2@upmc.edu.ORCID 0000-0003-4648-0735
Ricardo FerrariDivision of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Xiangdong CuiDivision of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Abish PiusMcGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.
Amrita SahuMcGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.
Michael ReynoldsDepartment of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.
Hong LiaoDivision of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Ping SunDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Sunita ShindeMcGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.
Fabrisia AmbrosioMcGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.
Sruti ShivaDepartment of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.
Patricia LoughranCenter for Biologic Imaging (CBI), University of Pittsburgh Medical Center, Biomedical Sciences Tower, Pittsburgh, PA, 15213, USA.
Melanie ScottDivision of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
University of Pittsburgh Medical Center · USMagee-Womens Hospital · USUnion Hospital · CN

Funding

VARIABILITY, STABILITY & SMOOTHNESS OF WALKINGP30AG024827 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Caterina Rosano · 2004 to 2026
$28.6M
Inflammasome activation in trauma-hemorrhagic shockR01GM102146 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCOTT, MELANIE J. · 2013 to 2025
$4.3M
Mechanisms of HMGB1 Release from Ischemic Muscle in Peripheral Arterial DiseaseR01HL136556 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SACHDEV, ULKA · 2018 to 2022
$2.0M
NHLBI NIH HHS R01 HL136556NHLBI NIH HHS R01HL136556NIA NIH HHS P30 AG024827NIGMS NIH HHS R01 GM102146NIGMS NIH HHS R01GM102146
6 · The paper itself

Abstract

backgroundWe previously showed that the autophagy inhibitor chloroquine (CQ) increases inflammatory cleaved caspase-1 activity in myocytes, and that caspase-1/11 is protective in sterile liver injury. However, the role of caspase-1/11 in the recovery of muscle from ischemia caused by peripheral arterial disease is unknown. We hypothesized that caspase-1/11 mediates recovery in muscle via effects on autophagy and this is modulated by CQ.

methodsC57Bl/6 J (WT) and caspase-1/11 double-knockout (KO) mice underwent femoral artery ligation (a model of hind-limb ischemia) with or without CQ (50 mg/kg IP every 2nd day). CQ effects on autophagosome formation, microtubule associated protein 1A/1B-light chain 3 (LC3), and caspase-1 expression was measured using electron microscopy and immunofluorescence. Laser Doppler perfusion imaging documented perfusion every 7 days. After 21 days, in situ physiologic testing in tibialis anterior muscle assessed peak force contraction, and myocyte size and fibrosis was also measured. Muscle satellite cell (MuSC) oxygen consumption rate (OCR) and extracellular acidification rate was measured. Caspase-1 and glycolytic enzyme expression was detected by Western blot.

resultsCQ increased autophagosomes, LC3 consolidation, total caspase-1 expression and cleaved caspase-1 in muscle. Perfusion, fibrosis, myofiber regeneration, muscle contraction, MuSC fusion, OCR, ECAR and glycolytic enzyme expression was variably affected by CQ depending on presence of caspase-1/11. CQ decreased perfusion recovery, fibrosis and myofiber size in WT but not caspase-1/11KO mice. CQ diminished peak force in whole muscle, and myocyte fusion in MuSC and these effects were exacerbated in caspase-1/11KO mice. CQ reductions in maximal respiration and ATP production were reduced in caspase-1/11KO mice. Caspase-1/11KO MuSC had significant increases in protein kinase isoforms and aldolase with decreased ECAR.

conclusionCaspase-1/11 signaling affects the response to ischemia in muscle and effects are variably modulated by CQ. This may be critically important for disease treated with CQ and its derivatives, including novel viral diseases (e.g. COVID-19) that are expected to affect patients with comorbidities like cardiovascular disease.

Indexed as

AnimalsAutophagosomesAutophagyBetacoronavirusCaspase 1Caspases, InitiatorChloroquineCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentGlycolysisIschemiaMaleMiceMice, Inbred C57BLMice, KnockoutCasp1 protein, mouseCasp4 protein, mouseCaspase 1Caspases, InitiatorChloroquineMap1lc3b protein, mouseMicrotubule-Associated ProteinsAutophagyGlycolysisInflammasomeIschemic muscleLysosomal inhibitionOxidative phosphorylation

Identifiers

PMID32641037
PMCPMC7341481
OpenAlexW3041733813

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.