An important safety consideration in the use of antagonists of myostatin and activins is whether these drugs induce myocardial hypertrophy and impair cardiac function. The current study evaluated the effects of a soluble ActRIIB receptor Fc fusion protein (ActRIIB.Fc), a ligand trap for TGF-β/activin family members including myostatin, on myocardial mass and function in simian immunodeficiency virus (SIV)-infected juvenile rhesus macaques (Macaca mulatta). Fourteen pair-housed, juvenile male rhesus macaques were inoculated with SIVmac239; 4 weeks postinoculation, they were treated with weekly injections of 10 mg/kg ActRIIB.Fc or saline for 12 weeks. Myocardial mass and function were evaluated using two-dimensional echocardiography at baseline and after 12 weeks. The administration of ActRIIB.Fc was associated with a significantly greater increase in thickness of left ventricular posterior wall and interventricular septum both in diastole and systole. Cardiac output and cardiac index increased with time, more in animals treated with ActRIIB.Fc than in those treated with saline, but the difference was not statistically significant. The changes in ejection fraction, fractional shortening, and stroke volume did not differ significantly between groups. The changes in end-diastolic and end-systolic volumes did not differ between groups. In addition to a large reduction in IGF1 mRNA expression in the ActRIIB.Fc-treated animals, complex changes were detected in the myocardial expression of proteins related to calcium transport and storage. In conclusion, ActRIIB.Fc administration for 12 weeks was associated with increased myocardial mass but did not adversely affect myocardial function in juvenile SIV-infected rhesus macaques. Further studies are necessary to establish long-term cardiac safety.
Pubmed ID: 30019021 RIS Download
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Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
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View all literature mentionsThis monoclonal targets calsequestrin 1 (D-10)
View all literature mentionsThis monoclonal targets PKA C-alpha (D38C6) Rabbit mAb
View all literature mentionsThis monoclonal targets ATP2A1/SERCA1
View all literature mentionsThis polyclonal targets Phospho-Phospholamban (Ser16/Thr17)
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Phospho-PKA C (Thr197) (D45D3) Rabbit mAb
View all literature mentionsThis monoclonal targets ATP2A2/SERCA2 (D51B11) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-PKA C (Thr197) (D45D3) Rabbit mAb
View all literature mentionsThis monoclonal targets PKA C-alpha (D38C6) Rabbit mAb
View all literature mentionsThis monoclonal targets ATP2A1/SERCA1
View all literature mentionsThis polyclonal targets Phospho-Phospholamban (Ser16/Thr17)
View all literature mentionsThis polyclonal targets Phospholamban
View all literature mentionsThis monoclonal targets calsequestrin 1 (D-10)
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