Cardiac Specific Overexpression of hHole Attenuates Isoproterenol–Induced Hypertrophic Remodeling through Inhibition of Extracellular Signal-Regulated Kinases (ERKs) Signalling
2016
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.
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