RGD Reference Report - Systemic Blockade of ACVR2B Ligands Protects Myocardium from Acute Ischemia-Reperfusion Injury. - Rat Genome Database

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Systemic Blockade of ACVR2B Ligands Protects Myocardium from Acute Ischemia-Reperfusion Injury.

Authors: Magga, Johanna  Vainio, Laura  Kilpiö, Teemu  Hulmi, Juha J  Taponen, Saija  Lin, Ruizhu  Räsänen, Markus  Szabó, Zoltán  Gao, Erhe  Rahtu-Korpela, Lea  Alakoski, Tarja  Ulvila, Johanna  Laitinen, Mika  Pasternack, Arja  Koch, Walter J  Alitalo, Kari  Kivelä, Riikka  Ritvos, Olli  Kerkelä, Risto 
Citation: Magga J, etal., Mol Ther. 2019 Mar 6;27(3):600-610. doi: 10.1016/j.ymthe.2019.01.013. Epub 2019 Jan 24.
RGD ID: 329849112
Pubmed: PMID:30765322   (View Abstract at PubMed)
PMCID: PMC6404100   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ymthe.2019.01.013   (Journal Full-text)

Activin A and myostatin, members of the transforming growth factor (TGF)-β superfamily of secreted factors, are potent negative regulators of muscle growth, but their contribution to myocardial ischemia-reperfusion (IR) injury is not known. The aim of this study was to investigate if activin 2B (ACVR2B) receptor ligands contribute to myocardial IR injury. Mice were treated with soluble ACVR2B decoy receptor (ACVR2B-Fc) and subjected to myocardial ischemia followed by reperfusion for 6 or 24 h. Systemic blockade of ACVR2B ligands by ACVR2B-Fc was protective against cardiac IR injury, as evidenced by reduced infarcted area, apoptosis, and autophagy and better preserved LV systolic function following IR. ACVR2B-Fc modified cardiac metabolism, LV mitochondrial respiration, as well as cardiac phenotype toward physiological hypertrophy. Similar to its protective role in IR injury in vivo, ACVR2B-Fc antagonized SMAD2 signaling and cell death in cardiomyocytes that were subjected to hypoxic stress. ACVR2B ligand myostatin was found to exacerbate hypoxic stress. In addition to acute cardioprotection in ischemia, ACVR2B-Fc provided beneficial effects on cardiac function in prolonged cardiac stress in cardiotoxicity model. By blocking myostatin, ACVR2B-Fc potentially reduces cardiomyocyte death and modifies cardiomyocyte metabolism for hypoxic conditions to protect the heart from IR injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACVR2BHumanAnthracycline-induced Cardiotoxicity treatmentIMP human construct in mouse modelRGD 
Acvr2bRatAnthracycline-induced Cardiotoxicity treatmentISOACVR2B (Homo sapiens)human construct in mouse modelRGD 
Acvr2bMouseAnthracycline-induced Cardiotoxicity treatmentISOACVR2B (Homo sapiens)human construct in mouse modelRGD 
ACVR2BHumanMyocardial Reperfusion Injury  ISOAcvr2b (Mus musculus)mRNA and protein:decreased expression:heart (mouse)RGD 
ACVR2BHumanMyocardial Reperfusion Injury treatmentIMP human construct in mouse modelRGD 
Acvr2bMouseMyocardial Reperfusion Injury  IEP mRNA and protein:decreased expression:heart (mouse)RGD 
Acvr2bMouseMyocardial Reperfusion Injury treatmentISOACVR2B (Homo sapiens)human construct in mouse modelRGD 
Acvr2bRatMyocardial Reperfusion Injury treatmentISOACVR2B (Homo sapiens)human construct in mouse modelRGD 
Acvr2bRatMyocardial Reperfusion Injury  ISOAcvr2b (Mus musculus)mRNA and protein:decreased expression:heart (mouse)RGD 
GDF11HumanMyocardial Reperfusion Injury  ISOGdf11 (Mus musculus)mRNA and protein:decreased expression:heart (mouse)RGD 
Gdf11RatMyocardial Reperfusion Injury  ISOGdf11 (Mus musculus)mRNA and protein:decreased expression:heart (mouse)RGD 
Gdf11MouseMyocardial Reperfusion Injury  IEP mRNA and protein:decreased expression:heart (mouse)RGD 
INHBAHumanMyocardial Reperfusion Injury  ISOInhba (Mus musculus)mRNA and protein:increased expression:heart (mouse)RGD 
InhbaRatMyocardial Reperfusion Injury  ISOInhba (Mus musculus)mRNA and protein:increased expression:heart (mouse)RGD 
InhbaMouseMyocardial Reperfusion Injury  IEP mRNA and protein:increased expression:heart (mouse)RGD 
MSTNHumanMyocardial Reperfusion Injury  ISOMstn (Mus musculus)mRNA and protein:increased expression:heart (mouse)RGD 
MstnRatMyocardial Reperfusion Injury  ISOMstn (Mus musculus)mRNA and protein:increased expression:heart (mouse)RGD 
MstnMouseMyocardial Reperfusion Injury  IEP mRNA and protein:increased expression:heart (mouse)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
InhbaRatcellular response to hypoxia  IEP  RGD 
MstnRatcellular response to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acvr2b  (activin A receptor type 2B)
Gdf11  (growth differentiation factor 11)
Inhba  (inhibin subunit beta A)
Mstn  (myostatin)

Genes (Mus musculus)
Acvr2b  (activin receptor IIB)
Gdf11  (growth differentiation factor 11)
Inhba  (inhibin beta-A)
Mstn  (myostatin)

Genes (Homo sapiens)
ACVR2B  (activin A receptor type 2B)
GDF11  (growth differentiation factor 11)
INHBA  (inhibin subunit beta A)
MSTN  (myostatin)


Additional Information