Title:Cardiac Specific Overexpression of hHole Attenuates Isoproterenol–Induced Hypertrophic Remodeling through Inhibition of Extracellular Signal-Regulated Kinases (ERKs) Signalling
Volume: 16
Issue: 5
Author(s): X. Ye, Y. Li, X. Wu, X. Mo, X. Fan, S. Luo, G. Dai, X. Wang, F. Chen, Y. Deng, X. Peng, Y. Wan, W. Xu, Z. Jiang, Q. Zeng, L. Cao, Y. Shi, X. Liu, W. Yuan, S. Zhang, X. Zhu, J. Zhou and Y. Wang
Affiliation:
Keywords:
Cardiac hypertrophy, human Hole gene (hHole), isoproterenol (ISO), extracellular signal-regulated
kinases (ERKs).
Abstract: The human Hole gene (hHole) encodes a six-transmembrane protein with 319-
amino acids. Our previous study showed that hHole was strongly expressed in adult heart
and may act as a suppressor of extracellular signal-regulated kinases (ERKs), overactivation
of which contributed to pathological cardiac hypertrophy. In this study, it was observed that
Hole expression was up-regulated in murine hypertrophic hearts. In a cardiac specific transgenic mouse
model, it was observed that overexpression of hHole specifically in heart attenuated cardiac hypertrophy and
fibrosis induced by isoproterenol (ISO), with blunted transcriptions of ERK1/2, total ERK1/2 proteins and
phosphorylated ERK1/2 (p-ERK1/2) levels. Furthermore, overexpression of hHole in mice by hydrodynamic
tail-vein injection with hHole plamids also inhibited cardiac hypertrophy induced by ISO. Our work identified
hHole as a novel repressor of cardiac hypertrophy, and provided new insights into the possible target for the
prevention or treatment of cardiac diseases.
