Project Grant R01HL180489

The National Heart, Lung, and Blood Institute awarded The Regents of the University of Colorado, doing business as University of Colorado-Denver, $572,539 on August 15, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to define histone deacetylase 8 (HDAC8) regulation of cardiac myofilament relaxation.

The research addresses diastolic dysfunction, which is characterized by slower cardiac relaxation and has proven difficult to treat pharmacologically due to complexity involving increased fibrosis, impaired calcium handling, and sarcomeric dysfunction. The project investigates how post-translational modifications of sarcomeric proteins—particularly acetylation of lysine residues—control myofilament relaxation kinetics. Preliminary data from the recipient's laboratory demonstrate that selective HDAC8 inhibition leads to faster myofilament and cardiomyocyte relaxation. Initial screening identified four lysines in the troponin complex that show higher acetylation when cardiomyocytes are treated with a selective HDAC8 inhibitor. The primary objective is to define the mechanisms by which HDAC8 modulates myofilament relaxation. Aim 1 will evaluate how acetylation at the four identified lysine sites in troponin affects myofilament relaxation using ex vivo and in vitro approaches to modify acetylation and measure relaxation kinetics.

Performance occurs in Aurora, Colorado. The period of performance extends from the award date through April 30, 2030. This is a Project Grant, the standard NIH R01 mechanism for investigator-initiated research.