Disruption of the sEH Gene Does Not Prevent Hypoxia‐Induced Right Ventricular Hypertrophy in Mice

Abstract

It is reported that disruption of the sEH gene in mice decreases blood pressure and protects against ischemia/reperfusion injury in the brain and heart. Others found that sEH disruption reduced survival due to cardiac arrest in mice. We tested the hypothesis that disruption of sEH in mice protects against the development of hypoxia‐induced right ventricular hypertrophy (RVH). Cardiac magnetic resonance (CMR) imaging was conducted on wild‐type (WT) and sEH knockout (KO) mice housed under the hypoxia (10% O2) condition for 5 weeks. Serial short‐axis MR images of heart from apex to base covering both right (RV) and left ventricles (LV) were captured in real time. From these images, RV and LV end diastole volumes, ejection fraction and wall thickness were determined. Following 5 wks of hypoxia, WT mice developed hypoxia‐induced RVH characterized by enlarged RV volume, increased wall thickness and reduced ejection fraction. The KO mice also developed RVH under the same conditions, similar cardiac structural and functional changes as that of WT mice. Exposure to hypoxia for 5 wks had no impact on LV structure and function in WT mice. However, 7 out of 9 KO mice survived hypoxia while all WT mice survived. Among the 7, 2 KO mice showed enlarged LV end‐diastole volume accompanied by reduced ejection fraction. In summary, our data revealed that sEH deficiency is not cardio‐protective when mice are challenged with hypoxia.