Author + information
- Xiaoyan Yang,
- Changlong Zheng,
- Caiqian Liang and
- Yongbiao Zhang
We aimed to observe the effects of cytochrome P450 epoxygenase 2J2 (CYP2J2) overexpression on right ventricular remodelling in monocrotaline-induced pulmonary hypertension in rats.
Forty SD rats were randomly divided into normal control group (NC group), monocrotaline group (MCT group), pCB6-treated group (MCT+pCB6 group) and pCB6-CYP2J2-treated group (MCT+2J2 group). MCT group, MCT+pCB6 group and MCT+2J2 group were given 60mg/kg MCT by subcutaneous injection. Three weeks after MCT injection, MCT+pCB6 group and MCT+2J2 group were injected either with a single intravenous dose of empty pCB6 vector or with pCB6-2J2 plasmid (3mg/kg body weight). Two weeks after gene delivery, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI, calculated by the ratio of right ventricle to the left ventricle plus septum) were detected. Collagen deposition was estimated in right ventricle sections after collagen I immunostaining and Sirius red staining. The expression levels of 2J2, transforming growth factor-β1(TGF-β1), phosphorylated Smad 3 (p-Smad3) and Smad 3 in the right ventricles in rats were detected by western blot.
The expression of CYP2J2 obviously increased in heart tissues in MCT+2J2 group but not in the MCT+pCB6 group. Five weeks after the injections of MCT, RVSP (82.4±8.4 vs 30.5± 2.8 mmHg, P<0.01) and RVHI (0.50±0.03 vs 0.24±0.01, P<0.01) in the MCT group were significantly elevated compared with those in the control group. Treatment with pCB6-2J2 but not with empty pCB6 vector significantly inhibited the elevation of RVSP (56.5±2.3 vs 80.8±7.8 mmHg, P<0.01) and RVHI (0.39 ± 0.02 vs 0.53 ± 0.04, P<0.01). Collagen I and Sirius red staining showed that striking collagen deposition in right ventricle of rats in the MCT group and pCB6 group. However, gene therapy with CYP2J2 significantly attenuated collagen deposition. Furthermore, MCT injection resulted in remarkably increases of TGF-β1 and p-smad3 expression in the MCT group and MCT+pCB6 group (P<0.01). In contrast, these changes were dramatically attenuated in MCT+2J2 group (P<0.01).
Our findings suggested that overexpression of CYP2J2 attenuated right ventricular remodelling in monocrotaline-induced pulmonary hypertension in rats. The results might be associated with the inhibition of expression of TGF-β1/smad3 signaling.