OGFOD1 Regulates Translation to Alter Hypertrophy Susceptibility

Cardiac hypertrophy, a precursor for heart failure, requires increased translation. However, little is known of the mechanisms that regulate translation in hypertrophy. Members of the 2-oxoglutarate-dependent dioxygenase family regulate several aspects of gene expression, including translation. An important member of this family is OGFOD1. Here, we show OGFOD1 accumulates in failing human hearts. Upon OGFOD1 deletion, murine hearts showed transcriptomic and proteomic changes, with only 21 factors (0.6%) changing in the same direction at both the mRNA and protein levels. Additionally, OGFOD1-KO mice were protected from induced hypertrophy, supporting a role for OGFOD1 in the cardiac response to chronic stress. Overall design: WT and OGFOD1-KO mice aged 3-5 months were treated with either vehicle (1X PBS and Sodium Ascorbate) or isoproterenol (1X PBS, Sodium Ascorbate, and Isoproterenol) for 2 weeks by osmotic minipump. Hearts were isolated from these mice and RNA was extracted and subjected to RNAsequencing.