dATP elevation induces myocardial metabolic remodeling to support improved cardiac function

Hallmark features of systolic heart failure are reduced contractility and impaired metabolic flexibility of the myocardium. Cardiomyocytes (CMs) with elevated deoxy ATP (dATP) via overexpression of ribonucleotide reductase (RNR) enzyme robustly improve contractility. However, the effect of dATP elevation on cardiac metabolism is unknown. Here, we developed proteolysis-resistant versions of RNR and demonstrate that elevation of dATP/ATP to ~1% in CMs in a transgenic mouse (TgRRB) resulted in robust improvement of cardiac function.

Source: Journal of Molecular and Cellular Cardiology - December 2, 2022 Category: Cytology Authors: Ketaki N. Mhatre, Jason D. Murray, Galina Flint, Timothy S. McMillen, Gerhard Weber, Majid Shakeri, An-Yue Tu, Sonette Steczina, Robert Weiss, David J. Marcinek, Charles E. Murry, Daniel Raftery, Rong Tian, Farid Moussavi-Harami, Michael Regnier Source Type: research