Urea Transporter B Gene Knockout Enhances Cardiac Hypertrophy Induced by Pressure Overload via NO and ROS Imbalance

Abstract

Objective: Urea transporter-B (UT-B) shows high expression in the heart; However, its role in cardiac hypertrophy remains unknown. This study aimed to investigate the role and mechanism of action of UT-B in cardiac hypertrophy induced by pressure overload. Methods: 16-week-old UT-B knockout and wild-type mice were used in this study. A cardiac hypertrophy model was established by abdominal aorta banding. Echocardiography, histology, hematoxylin and eosin staining, and western blotting were conducted to evaluate cardiac function, morphology, nitric oxide (NO) synthesis, and oxidative stress. Proteasome activities were also examined using a fluorescent peptide substrate. Results: Systolic functional parameters [Ejection fraction (EF), Fractional shortening (FS)] and diastolic functional parameters [ratio of E peak to A peak (E/A)] did not change significantly in UT-B knockout mice compared with those in wild-type mice, but they were decreased significantly after abdominal aorta banding in UT-B knockout mice. Moreover, UT-B knockout mice showed increased heart volume and atrial natriuretic peptide (ANP) expression after abdominal aortic banding. Moreover, reactive oxygen species (ROS) and malondialdehyde levels were upregulated in UT-B knockout mice and were further increased after abdominal aorta banding, whereas the antioxidant enzyme activity was downregulated. In addition, nitric NO levels and endothelial nitric oxide synthase (eNOS) expression were downregulated in UT-B knockout mice and were further decreased after abdominal aorta banding. Conclusions: UT-B knockout enhances cardiac hypertrophy induced by abdominal aorta banding via upregulation of ROS levels and downregulation of NO levels in the heart tissue, suggesting that UT-B plays an important role in the maintenance of cardiac function.