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Magga 2019 Mol Ther
Additional label 2019-02  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Diseases Cardiovascular  + , Myopathy  +
Has abstract Activin A and myostatin, members of the tr
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.
tions to protect the heart from IR injury.  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30765322 Open Access]  +
Has publicationkeywords Activins  + , ACVR2B  + , Growth differentiation factors  + , Ischemia-reperfusion injury  +
Has title Magga J, Vainio L, Kilpiö T, Hulmi JJ, Tap
Magga J, Vainio L, Kilpiö T, Hulmi JJ, Taponen S, Lin R, Räsänen M, Szabó Z, Gao E, Rahtu-Korpela L, Alakoski T, Ulvila J, Laitinen M, Pasternack A, Koch WJ, Alitalo K, Kivelä R, Ritvos O, Kerkelä R (2019) Systemic blockade of ACVR2B ligands protects myocardium from acute ischemia-reperfusion injury. Mol Ther 27:600-10.
ia-reperfusion injury. Mol Ther 27:600-10.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Pharmacology;toxicology  +
Pathways N  + , S  + , NS  +
Preparation Homogenate  +
Stress Ischemia-reperfusion  +
Tissue and cell Heart  +
Was published in journal Mol Ther +
Was published in year 2019  +
Was written by Magga J + , Vainio L + , Kilpioe T + , Hulmi JJ + , Taponen S + , Lin R + , Raesaenen M + , Szabo Z + , Gao E + , Rahtu-Korpela L + , Alakoski T + , Ulvila J + , Laitinen M + , Pasternack A + , Koch WJ + , Alitalo K + , Kivelae R + , Ritvos O + , Kerkelae R +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
09:46:24, 25 July 2019  +
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