HDAC Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling
Circulation2021Vol. 143(19), pp. 1874–1890
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Joshua G. Travers, Sara A. Wennersten, Brisa Peña, Rushita A. Bagchi, Harrison E. Smith, Rachel Hirsch, Lauren A. Vanderlinden, Ying‐Hsi Lin, Evgenia Dobrinskikh, Kimberly Demos-Davies, Maria A. Cavasin, Luisa Mestroni, Christian Steinkühler, Charles Y. Lin, Steven R. Houser, Kathleen C. Woulfe, Maggie P. Y. Lam, Timothy A. McKinsey
Abstract
These findings demonstrate the potential of HDAC inhibition as a therapeutic intervention to reverse existing DD and establish blockade of extracellular matrix remodeling as a second mechanism by which HDAC inhibitors improve ventricular filling. Our data reveal the existence of pathophysiologically relevant covert or hidden cardiac fibrosis that is below the limit of detection of histochemical stains such as picrosirius red, highlighting the need to evaluate fibrosis of the heart using diverse methodologies.
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