Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine.
Identifieur interne : 000062 ( Main/Corpus ); précédent : 000061; suivant : 000063Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine.
Auteurs : Ulka Sachdev ; Ricardo Ferrari ; Xiangdong Cui ; Abish Pius ; Amrita Sahu ; Michael Reynolds ; Hong Liao ; Ping Sun ; Sunita Shinde ; Fabrisia Ambrosio ; Sruti Shiva ; Patricia Loughran ; Melanie ScottSource :
- Molecular medicine (Cambridge, Mass.) [ 1528-3658 ] ; 2020.
English descriptors
- KwdEn :
- Animals (MeSH), Autophagosomes (metabolism), Autophagy (drug effects), Betacoronavirus (MeSH), Caspase 1 (metabolism), Caspases, Initiator (metabolism), Chloroquine (pharmacology), Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Glycolysis (physiology), Ischemia (pathology), Male (MeSH), Mice (MeSH), Mice, Inbred C57BL (MeSH), Mice, Knockout (MeSH), Microtubule-Associated Proteins (metabolism), Muscle Cells (metabolism), Muscle Development (MeSH), Muscle, Skeletal (metabolism), Muscle, Skeletal (pathology), Neovascularization, Physiologic (MeSH), Oxidative Phosphorylation (MeSH), Pandemics (MeSH), Peripheral Arterial Disease (pathology), Pneumonia, Viral (drug therapy), Pneumonia, Viral (pathology), Regeneration (MeSH), Signal Transduction (MeSH).
- MESH :
- chemical , metabolism : Caspase 1, Caspases, Initiator, Microtubule-Associated Proteins.
- drug effects : Autophagy.
- drug therapy : Coronavirus Infections, Pneumonia, Viral.
- metabolism : Autophagosomes, Muscle Cells, Muscle, Skeletal.
- pathology : Coronavirus Infections, Ischemia, Muscle, Skeletal, Peripheral Arterial Disease, Pneumonia, Viral.
- chemical , pharmacology : Chloroquine.
- physiology : Glycolysis.
- Animals, Betacoronavirus, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Development, Neovascularization, Physiologic, Oxidative Phosphorylation, Pandemics, Regeneration, Signal Transduction.
Abstract
BACKGROUND
We 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.
METHODS
C57Bl/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.
RESULTS
CQ 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.
CONCLUSION
Caspase-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.
DOI: 10.1186/s10020-020-00190-2
PubMed: 32641037
PubMed Central: PMC7341481
Links to Exploration step
pubmed:32641037Le document en format XML
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Sachdevu2@upmc.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Ferrari, Ricardo" sort="Ferrari, Ricardo" uniqKey="Ferrari R" first="Ricardo" last="Ferrari">Ricardo Ferrari</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cui, Xiangdong" sort="Cui, Xiangdong" uniqKey="Cui X" first="Xiangdong" last="Cui">Xiangdong Cui</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Pius, Abish" sort="Pius, Abish" uniqKey="Pius A" first="Abish" last="Pius">Abish Pius</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sahu, Amrita" sort="Sahu, Amrita" uniqKey="Sahu A" first="Amrita" last="Sahu">Amrita Sahu</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Reynolds, Michael" sort="Reynolds, Michael" uniqKey="Reynolds M" first="Michael" last="Reynolds">Michael Reynolds</name><affiliation><nlm:affiliation>Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Liao, Hong" sort="Liao, Hong" uniqKey="Liao H" first="Hong" last="Liao">Hong Liao</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, Ping" sort="Sun, Ping" uniqKey="Sun P" first="Ping" last="Sun">Ping Sun</name><affiliation><nlm:affiliation>Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Surgery 11/20/2018-11/19/202, Visiting scholar, University of Pittsburgh, Pittsburgh, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shinde, Sunita" sort="Shinde, Sunita" uniqKey="Shinde S" first="Sunita" last="Shinde">Sunita Shinde</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ambrosio, Fabrisia" sort="Ambrosio, Fabrisia" uniqKey="Ambrosio F" first="Fabrisia" last="Ambrosio">Fabrisia Ambrosio</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shiva, Sruti" sort="Shiva, Sruti" uniqKey="Shiva S" first="Sruti" last="Shiva">Sruti Shiva</name><affiliation><nlm:affiliation>Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Loughran, Patricia" sort="Loughran, Patricia" uniqKey="Loughran P" first="Patricia" last="Loughran">Patricia Loughran</name><affiliation><nlm:affiliation>Center for Biologic Imaging (CBI), University of Pittsburgh Medical Center, Biomedical Sciences Tower, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Scott, Melanie" sort="Scott, Melanie" uniqKey="Scott M" first="Melanie" last="Scott">Melanie Scott</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32641037</idno><idno type="pmid">32641037</idno><idno type="doi">10.1186/s10020-020-00190-2</idno><idno type="pmc">PMC7341481</idno><idno type="wicri:Area/Main/Corpus">000062</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000062</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine.</title><author><name sortKey="Sachdev, Ulka" sort="Sachdev, Ulka" uniqKey="Sachdev U" first="Ulka" last="Sachdev">Ulka Sachdev</name><affiliation><nlm:affiliation>Division 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.</nlm:affiliation></affiliation></author><author><name sortKey="Ferrari, Ricardo" sort="Ferrari, Ricardo" uniqKey="Ferrari R" first="Ricardo" last="Ferrari">Ricardo Ferrari</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cui, Xiangdong" sort="Cui, Xiangdong" uniqKey="Cui X" first="Xiangdong" last="Cui">Xiangdong Cui</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Pius, Abish" sort="Pius, Abish" uniqKey="Pius A" first="Abish" last="Pius">Abish Pius</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sahu, Amrita" sort="Sahu, Amrita" uniqKey="Sahu A" first="Amrita" last="Sahu">Amrita Sahu</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Reynolds, Michael" sort="Reynolds, Michael" uniqKey="Reynolds M" first="Michael" last="Reynolds">Michael Reynolds</name><affiliation><nlm:affiliation>Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Liao, Hong" sort="Liao, Hong" uniqKey="Liao H" first="Hong" last="Liao">Hong Liao</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, Ping" sort="Sun, Ping" uniqKey="Sun P" first="Ping" last="Sun">Ping Sun</name><affiliation><nlm:affiliation>Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Surgery 11/20/2018-11/19/202, Visiting scholar, University of Pittsburgh, Pittsburgh, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shinde, Sunita" sort="Shinde, Sunita" uniqKey="Shinde S" first="Sunita" last="Shinde">Sunita Shinde</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ambrosio, Fabrisia" sort="Ambrosio, Fabrisia" uniqKey="Ambrosio F" first="Fabrisia" last="Ambrosio">Fabrisia Ambrosio</name><affiliation><nlm:affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shiva, Sruti" sort="Shiva, Sruti" uniqKey="Shiva S" first="Sruti" last="Shiva">Sruti Shiva</name><affiliation><nlm:affiliation>Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Loughran, Patricia" sort="Loughran, Patricia" uniqKey="Loughran P" first="Patricia" last="Loughran">Patricia Loughran</name><affiliation><nlm:affiliation>Center for Biologic Imaging (CBI), University of Pittsburgh Medical Center, Biomedical Sciences Tower, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Scott, Melanie" sort="Scott, Melanie" uniqKey="Scott M" first="Melanie" last="Scott">Melanie Scott</name><affiliation><nlm:affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Molecular medicine (Cambridge, Mass.)</title><idno type="eISSN">1528-3658</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Autophagosomes (metabolism)</term><term>Autophagy (drug effects)</term><term>Betacoronavirus (MeSH)</term><term>Caspase 1 (metabolism)</term><term>Caspases, Initiator (metabolism)</term><term>Chloroquine (pharmacology)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (pathology)</term><term>Glycolysis (physiology)</term><term>Ischemia (pathology)</term><term>Male (MeSH)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Mice, Knockout (MeSH)</term><term>Microtubule-Associated Proteins (metabolism)</term><term>Muscle Cells (metabolism)</term><term>Muscle Development (MeSH)</term><term>Muscle, Skeletal (metabolism)</term><term>Muscle, Skeletal (pathology)</term><term>Neovascularization, Physiologic (MeSH)</term><term>Oxidative Phosphorylation (MeSH)</term><term>Pandemics (MeSH)</term><term>Peripheral Arterial Disease (pathology)</term><term>Pneumonia, Viral (drug therapy)</term><term>Pneumonia, Viral (pathology)</term><term>Regeneration (MeSH)</term><term>Signal Transduction (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Caspase 1</term><term>Caspases, Initiator</term><term>Microtubule-Associated Proteins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Autophagosomes</term><term>Muscle Cells</term><term>Muscle, Skeletal</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term><term>Ischemia</term><term>Muscle, Skeletal</term><term>Peripheral Arterial Disease</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Glycolysis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Betacoronavirus</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Muscle Development</term><term>Neovascularization, Physiologic</term><term>Oxidative Phosphorylation</term><term>Pandemics</term><term>Regeneration</term><term>Signal Transduction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>We 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.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>C57Bl/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.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>CQ 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.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Caspase-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.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32641037</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>20</Day></DateCompleted><DateRevised><Year>2020</Year><Month>07</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1528-3658</ISSN><JournalIssue CitedMedium="Internet"><Volume>26</Volume><Issue>1</Issue><PubDate><Year>2020</Year><Month>07</Month><Day>08</Day></PubDate></JournalIssue><Title>Molecular medicine (Cambridge, Mass.)</Title><ISOAbbreviation>Mol. Med.</ISOAbbreviation></Journal><ArticleTitle>Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine.</ArticleTitle><Pagination><MedlinePgn>69</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1186/s10020-020-00190-2</ELocationID><Abstract><AbstractText Label="BACKGROUND">We 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.</AbstractText><AbstractText Label="METHODS">C57Bl/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.</AbstractText><AbstractText Label="RESULTS">CQ 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.</AbstractText><AbstractText Label="CONCLUSION">Caspase-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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sachdev</LastName><ForeName>Ulka</ForeName><Initials>U</Initials><Identifier Source="ORCID">0000-0003-4648-0735</Identifier><AffiliationInfo><Affiliation>Division 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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferrari</LastName><ForeName>Ricardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Xiangdong</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pius</LastName><ForeName>Abish</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sahu</LastName><ForeName>Amrita</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reynolds</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Hong</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Ping</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Surgery 11/20/2018-11/19/202, Visiting scholar, University of Pittsburgh, Pittsburgh, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shinde</LastName><ForeName>Sunita</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ambrosio</LastName><ForeName>Fabrisia</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Bridgeside Point, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shiva</LastName><ForeName>Sruti</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Biomedical Sciences Towe, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Loughran</LastName><ForeName>Patricia</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Center for Biologic Imaging (CBI), University of Pittsburgh Medical Center, Biomedical Sciences Tower, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>Melanie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Vascular Surgery; Department of Surgery, University of Pittsburgh Medical Center, Magee Women's Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01HL136556</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01GM102146</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Mol Med</MedlineTA><NlmUniqueID>9501023</NlmUniqueID><ISSNLinking>1076-1551</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C480860">MAP1LC3 protein, 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