rhADAMTS13 treatment improves ventricular remodeling and functionality after cardiac injury in mice
T. Witsch1,2, K. Martinod2, D. D. Wagner2 (1Freiburg, Germany, 2Boston, USA)
Innovation and Novelty
Time: 14:00 - 15:15
Objective: Myocardial injury leads to detrimental cardiac remodeling, scar tissue formation and, eventually, congestive heart failure. Von Willebrand factor, released from the stimulated vessel wall, mediates leukocyte and platelet recruitment and thereby promotes coronary inflammation and micro-vessel thrombosis. The metalloproteinase ADAMTS13 decreases the size and activity of ultra-large VWF and its infusion produces beneficial results 24 hours after myocardial ischemia reperfusion injury (MIRI) in mice.
Methods: We evaluated the effect of recombinant human ADAMTS13 (rhADAMTS13) treatment on long-term cardiac remodeling and functionality in mice undergoing surgical models of MIRI and chronic left ventricular pressure overload. Both models produce a coronary inflammatory response and micro-vascular dysfunction. Mice were treated with either rhADAMTS13 or vehicle and assessed for myocardial inflammatory cell recruitment, ventricular function and dimensions at different post-surgical time points, and for cardiac fibrosis after 4 weeks.
Results: We observed significant preservation of cardiac function and decrease in fibrotic remodeling as a result of rhADAMTS13 treatment in both models of cardiac injury. Coronary vascular inflammation and inflammatory cell recruitment in pressure-overloaded ventricles was attenuated in rhADAMTS13 treated mice.
Conclusion: Here we show that rhADAMTS13 improves cardiac remodeling after injury by MIRI or left ventricular pressure overload in mice. Our study further supports the therapeutic potential of rhADAMTS13 for myocardial infarction patients in the future and, potentially, in other conditions characterized by inflammatory cardiac damage that results in fibrosis.