HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction
Markus Wallner, Deborah Eaton, Remus M. Berretta, Laura Liesinger, Matthias Schittmayer, Juergen Gindlhuber, Jichuan Wu, Mark Y. Jeong, Ying Lin, Giulia Borghetti, Sandy T. Baker, Huaqing Zhao, Jessica Pfleger, Sandra Blaß, Peter P. Rainer, Dirk von Lewinski, Heiko Bugger, Sadia Mohsin, Wolfgang F. Graier, Andreas Zirlik, Timothy A. McKinsey, Ruth Birner‐Gruenberger, Marla R. Wolfson, Steven R. Houser
Abstract
< 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and function in patients.