Loss of Cardiac Muscle Ring Finger‐1 Augments Right Ventricular Hypertrophy Following Chronic Hypoxia‐Induced Pulmonary Hypertension

Abstract

Exposure to chronic hypoxia (CH) induces elevated pulmonary artery pressure/resistance, leading to an eventual maladaptive right ventricular hypertrophy (RVH). Muscle RING‐finger (MuRF)1 is a muscle specific protein has been shown to play a role in left ventricular hypertrophy and altered cardiac bioenergetics in pressure overloaded hearts, however little is known about the contribution of MuRF1 impacting RVH in the setting of CH. Therefore, we hypothesized that MuRF1 deletion would enhance RVH compared to their wild‐type (WT) littermates following CH‐induced pulmonary hypertension. Thus, we assessed right ventricular systolic pressure (RVSP), right ventricle to left ventricle plus septal weight ratio (RV/LV+S) and hematocrit (Hct) following a 3 week isobaric CH exposure. CH induced pulmonary hypertension, measured by increases RVSP, RV/LV+S and Hct, WT mice compared to normoxic WT mice. Normoxic WT and MuRF1‐null mice exhibited no significant differences in RVSP, RV/LV+S or Hct. CH‐induced increases in RVSP were also similar between WT and MuRF1‐null mice; however, RV/LV+S and Hct were significantly elevated in CH‐exposed MuRF1‐null mice compared to WT. In conclusion, these results suggest an atrophic role for MuRF1 regulating the magnitude of right ventricular hypertrophy and polycythemia following CH‐induction of pulmonary hypertension.