Right ventricular (RV) remodeling is a major feature of
pulmonary arterial hypertension (PAH). Vascular
peroxidase 1 (VPO1) is reported to participate in the process of PAH. This study aims to explore whether VPO1 contributes to
hypoxia-induced
cardiac hypertrophy and the underlying mechanisms. SD rats were exposure to continuous
hypoxia (10% O2) for 3 weeks, which showed RV
hypertrophy (increases in the ratio of RV weight to tibia length, cardiac cell size and hypertrophic markers), concomitant with upregulation of VPO1, elevation in
hypochlorous acid (HOCl) production and ERK phosphorylation. In
hypoxia (3% O2)-induced hypertrophic H9c2 cells, similar characteristics of
cardiac hypertrophy to that of
hypoxia-treated rats were observed. Administration of VPO1
siRNA or
NaHS (the HOCl inhibitor) suppressed HOCl production, ERK phosphorylation, and
cardiac hypertrophy. Replacement of
hypoxia with NaClO (exogenous HOCl) could also induce cardiac cell
hypertrophy and activate ERK signaling pathway. In addition,
hypoxia-induced
cardiac hypertrophy could be blocked by
PD98059 (the ERK-specific inhibitor). Based on these observations, we conclude that VPO1 promotes RV remodeling in PAH rats through catalyzing HOCl production, leading to the activation of ERK signaling. Thus, VPO1 may have the potential as a therapeutic target for PAH.