Systemic blockade of ACVR2B ligands protects myocardium from acute ischemia-reperfusion injury

6533b824fe1ef96bd128027f

RESEARCH PRODUCT

Systemic blockade of ACVR2B ligands protects myocardium from acute ischemia-reperfusion injury

Risto Kerkelä Risto Kerkelä Mika Laitinen Erhe Gao Markus Räsänen Johanna Ulvila Walter J. Koch Johanna Magga Juha J. Hulmi Olli Ritvos Riikka Kivelä Tarja Alakoski Teemu Kilpiö Lea Rahtu-korpela Ruizhu Lin Kari Alitalo Arja Pasternack Zoltan Szabo Laura Vainio Saija Taponen

subject

Male Activin Receptors Type II iskemia lihakset Smad2 Protein Myostatin Pharmacology Mice 0302 clinical medicine Drug Discovery kasvutekijät Myocytes Cardiac Cardioprotection 0303 health sciences 318 Medical biotechnology biology sydän activins 1184 Genetics developmental biology physiology II RECEPTORS 3. Good health 030220 oncology & carcinogenesis Molecular Medicine Original Article Signal Transduction Cardiac function curve growth differentiation factors Programmed cell death BLOCKING ischemia-reperfusion injury Ischemia Myocardial Reperfusion Injury MASS ta3111 03 medical and health sciences MYOSTATIN-KNOCKOUT CARDIOPROTECTION Genetics medicine Animals Molecular Biology lihassolut 030304 developmental biology Pharmacology SKELETAL-MUSCLE GROWTH business.industry Myocardium FOLLISTATIN Myostatin medicine.disease ACVR2B Mice Inbred C57BL ACTIVIN-A GDF11 GDF11 biology.protein 3111 Biomedicine proteiinit business Reperfusion injury DIFFERENTIATION FACTOR 11 ACVR2B Transcription Factors

description

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.

year	journal	country	edition	language
2019-01-01

http://urn.fi/URN:NBN:fi:jyu-201903071776