Granzyme B Deficiency Protects against Angiotensin II-Induced Cardiac Fibrosis.
Identifieur interne : 000314 ( PubMed/Corpus ); précédent : 000313; suivant : 000315Granzyme B Deficiency Protects against Angiotensin II-Induced Cardiac Fibrosis.
Auteurs : Yue Shen ; Fang Cheng ; Mehul Sharma ; Yulia Merkulova ; Sheetal A. Raithatha ; Leigh G. Parkinson ; Hongyan Zhao ; Kathryn Westendorf ; Lubos Bohunek ; Tatjana Bozin ; Ivy Hsu ; Lisa S. Ang ; Sarah J. Williams ; R Chris Bleackley ; John E. Eriksson ; Michael A. Seidman ; Bruce M. Mcmanus ; David J. GranvilleSource :
- The American journal of pathology [ 1525-2191 ] ; 2016.
English descriptors
- KwdEn :
- Adult, Aged, Animals, Disease Models, Animal, Female, Fibrosis (enzymology), Fibrosis (pathology), Fluorescent Antibody Technique, Granzymes (metabolism), Heart Diseases (enzymology), Heart Diseases (pathology), Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Real-Time Polymerase Chain Reaction, Young Adult.
- MESH :
- chemical , metabolism : Granzymes.
- enzymology : Fibrosis, Heart Diseases.
- pathology : Fibrosis, Heart Diseases.
- Adult, Aged, Animals, Disease Models, Animal, Female, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Real-Time Polymerase Chain Reaction, Young Adult.
Abstract
Cardiac fibrosis is observed across diverse etiologies of heart failure. Granzyme B (GzmB) is a serine protease involved in cell-mediated cytotoxicity in conjunction with the pore-forming protein, perforin. Recent evidence suggests that GzmB also contributes to matrix remodeling and fibrosis through an extracellular, perforin-independent process. However, the role of GzmB in the onset and progression of cardiac fibrosis remains elusive. The present study investigated the role of GzmB in the pathogenesis of cardiac fibrosis. GzmB was elevated in fibrotic human hearts and in angiotensin II-induced murine cardiac fibrosis. Genetic deficiency of GzmB reduced angiotensin II-induced cardiac hypertrophy and fibrosis, independently of perforin. GzmB deficiency also reduced microhemorrhage, inflammation, and fibroblast accumulation in vivo. In vitro, GzmB cleaved the endothelial junction protein, vascular endothelial (VE)-cadherin, resulting in the disruption of endothelial barrier function. Together, these results suggest a perforin-independent, extracellular role for GzmB in the pathogenesis of cardiac fibrosis.
DOI: 10.1016/j.ajpath.2015.09.010
PubMed: 26610869
Links to Exploration step
pubmed:26610869Le document en format XML
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Williams</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bleackley, R Chris" sort="Bleackley, R Chris" uniqKey="Bleackley R" first="R Chris" last="Bleackley">R Chris Bleackley</name><affiliation><nlm:affiliation>Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Eriksson, John E" sort="Eriksson, John E" uniqKey="Eriksson J" first="John E" last="Eriksson">John E. Eriksson</name><affiliation><nlm:affiliation>Department of Biosciences, Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Seidman, Michael A" sort="Seidman, Michael A" uniqKey="Seidman M" first="Michael A" last="Seidman">Michael A. Seidman</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcmanus, Bruce M" sort="Mcmanus, Bruce M" uniqKey="Mcmanus B" first="Bruce M" last="Mcmanus">Bruce M. Mcmanus</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Granville, David J" sort="Granville, David J" uniqKey="Granville D" first="David J" last="Granville">David J. Granville</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 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Raithatha</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Parkinson, Leigh G" sort="Parkinson, Leigh G" uniqKey="Parkinson L" first="Leigh G" last="Parkinson">Leigh G. Parkinson</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Zhao, Hongyan" sort="Zhao, Hongyan" uniqKey="Zhao H" first="Hongyan" last="Zhao">Hongyan Zhao</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Westendorf, Kathryn" sort="Westendorf, Kathryn" uniqKey="Westendorf K" first="Kathryn" last="Westendorf">Kathryn Westendorf</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bohunek, Lubos" sort="Bohunek, Lubos" uniqKey="Bohunek L" first="Lubos" last="Bohunek">Lubos Bohunek</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bozin, Tatjana" sort="Bozin, Tatjana" uniqKey="Bozin T" first="Tatjana" last="Bozin">Tatjana Bozin</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Ivy" sort="Hsu, Ivy" uniqKey="Hsu I" first="Ivy" last="Hsu">Ivy Hsu</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Ang, Lisa S" sort="Ang, Lisa S" uniqKey="Ang L" first="Lisa S" last="Ang">Lisa S. Ang</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Williams, Sarah J" sort="Williams, Sarah J" uniqKey="Williams S" first="Sarah J" last="Williams">Sarah J. Williams</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bleackley, R Chris" sort="Bleackley, R Chris" uniqKey="Bleackley R" first="R Chris" last="Bleackley">R Chris Bleackley</name><affiliation><nlm:affiliation>Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Eriksson, John E" sort="Eriksson, John E" uniqKey="Eriksson J" first="John E" last="Eriksson">John E. Eriksson</name><affiliation><nlm:affiliation>Department of Biosciences, Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Seidman, Michael A" sort="Seidman, Michael A" uniqKey="Seidman M" first="Michael A" last="Seidman">Michael A. Seidman</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcmanus, Bruce M" sort="Mcmanus, Bruce M" uniqKey="Mcmanus B" first="Bruce M" last="Mcmanus">Bruce M. Mcmanus</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Granville, David J" sort="Granville, David J" uniqKey="Granville D" first="David J" last="Granville">David J. Granville</name><affiliation><nlm:affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: david.granville@hli.ubc.ca.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The American journal of pathology</title><idno type="eISSN">1525-2191</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Fibrosis (enzymology)</term><term>Fibrosis (pathology)</term><term>Fluorescent Antibody Technique</term><term>Granzymes (metabolism)</term><term>Heart Diseases (enzymology)</term><term>Heart Diseases (pathology)</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Middle Aged</term><term>Real-Time Polymerase Chain Reaction</term><term>Young Adult</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Granzymes</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Fibrosis</term><term>Heart Diseases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Fibrosis</term><term>Heart Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Fluorescent Antibody Technique</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Middle Aged</term><term>Real-Time Polymerase Chain Reaction</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cardiac fibrosis is observed across diverse etiologies of heart failure. Granzyme B (GzmB) is a serine protease involved in cell-mediated cytotoxicity in conjunction with the pore-forming protein, perforin. Recent evidence suggests that GzmB also contributes to matrix remodeling and fibrosis through an extracellular, perforin-independent process. However, the role of GzmB in the onset and progression of cardiac fibrosis remains elusive. The present study investigated the role of GzmB in the pathogenesis of cardiac fibrosis. GzmB was elevated in fibrotic human hearts and in angiotensin II-induced murine cardiac fibrosis. Genetic deficiency of GzmB reduced angiotensin II-induced cardiac hypertrophy and fibrosis, independently of perforin. GzmB deficiency also reduced microhemorrhage, inflammation, and fibroblast accumulation in vivo. In vitro, GzmB cleaved the endothelial junction protein, vascular endothelial (VE)-cadherin, resulting in the disruption of endothelial barrier function. Together, these results suggest a perforin-independent, extracellular role for GzmB in the pathogenesis of cardiac fibrosis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26610869</PMID><DateCreated><Year>2015</Year><Month>12</Month><Day>31</Day></DateCreated><DateCompleted><Year>2016</Year><Month>05</Month><Day>10</Day></DateCompleted><DateRevised><Year>2015</Year><Month>12</Month><Day>31</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1525-2191</ISSN><JournalIssue CitedMedium="Internet"><Volume>186</Volume><Issue>1</Issue><PubDate><Year>2016</Year><Month>Jan</Month></PubDate></JournalIssue><Title>The American journal of pathology</Title><ISOAbbreviation>Am. J. Pathol.</ISOAbbreviation></Journal><ArticleTitle>Granzyme B Deficiency Protects against Angiotensin II-Induced Cardiac Fibrosis.</ArticleTitle><Pagination><MedlinePgn>87-100</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ajpath.2015.09.010</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0002-9440(15)00572-6</ELocationID><Abstract><AbstractText>Cardiac fibrosis is observed across diverse etiologies of heart failure. Granzyme B (GzmB) is a serine protease involved in cell-mediated cytotoxicity in conjunction with the pore-forming protein, perforin. Recent evidence suggests that GzmB also contributes to matrix remodeling and fibrosis through an extracellular, perforin-independent process. However, the role of GzmB in the onset and progression of cardiac fibrosis remains elusive. The present study investigated the role of GzmB in the pathogenesis of cardiac fibrosis. GzmB was elevated in fibrotic human hearts and in angiotensin II-induced murine cardiac fibrosis. Genetic deficiency of GzmB reduced angiotensin II-induced cardiac hypertrophy and fibrosis, independently of perforin. GzmB deficiency also reduced microhemorrhage, inflammation, and fibroblast accumulation in vivo. In vitro, GzmB cleaved the endothelial junction protein, vascular endothelial (VE)-cadherin, resulting in the disruption of endothelial barrier function. Together, these results suggest a perforin-independent, extracellular role for GzmB in the pathogenesis of cardiac fibrosis.</AbstractText><CopyrightInformation>Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Yue</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Fang</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Biosciences, Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sharma</LastName><ForeName>Mehul</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Merkulova</LastName><ForeName>Yulia</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raithatha</LastName><ForeName>Sheetal A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Parkinson</LastName><ForeName>Leigh G</ForeName><Initials>LG</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Hongyan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Westendorf</LastName><ForeName>Kathryn</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bohunek</LastName><ForeName>Lubos</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bozin</LastName><ForeName>Tatjana</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hsu</LastName><ForeName>Ivy</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ang</LastName><ForeName>Lisa S</ForeName><Initials>LS</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Williams</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bleackley</LastName><ForeName>R Chris</ForeName><Initials>RC</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eriksson</LastName><ForeName>John E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Department of Biosciences, Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seidman</LastName><ForeName>Michael A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McManus</LastName><ForeName>Bruce M</ForeName><Initials>BM</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Granville</LastName><ForeName>David J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: david.granville@hli.ubc.ca.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MOP 133518</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant><Grant><GrantID>MOP 332654</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>11</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Am J Pathol</MedlineTA><NlmUniqueID>0370502</NlmUniqueID><ISSNLinking>0002-9440</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>EC 3.4.21.-</RegistryNumber><NameOfSubstance UI="D053804">Granzymes</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005355" MajorTopicYN="N">Fibrosis</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005455" MajorTopicYN="N">Fluorescent Antibody Technique</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053804" MajorTopicYN="N">Granzymes</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006331" MajorTopicYN="N">Heart Diseases</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D060888" MajorTopicYN="N">Real-Time Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>06</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>09</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>09</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>11</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>11</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>5</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26610869</ArticleId><ArticleId IdType="pii">S0002-9440(15)00572-6</ArticleId><ArticleId IdType="doi">10.1016/j.ajpath.2015.09.010</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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