Objective: To explore potential divergent glycolytic metabolism gene changes between left and right ventricle in the monocmtaline (MCT) induced pulmonary arterial hypertension (PAH) rat model.
Methods: PAH was induced by a single subcutaneous injection of MCT (50 mg/kg) in rats. Control rats were injected with normal saline. MCT-PAH rats were randomly divided into MCT-2week, MCT-3week and MCT-4week groups (MCT-2w, 3w, 4w). At the end of study, the hemodynamics and right ventricular hypertrophy were compared among groups. The expression levels of proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP nick end labeling (TUNEL) in left and right ventricular cells were compared. The glycolytic key candidate genes expression was screened between two ventricles.
Results: After three to four weeks MCT injection, mean pulmonary arterial pressure, right ventricular systolic pressure and right ventricular hypertrophy index were all significantly increased compared to control group (all P < 0.05). Both left and right ventricular morphology and structure changes were observed in all PAH rats and were similar between left and right ventricular cells. Left and right ventricular cells increased while apoptotic cells decreased in proportion to the duration post MCT injection and the PCNA positive cells in the right ventricle were higher than in the left ventricle in rats post 3 and 4 weeks MCT injection (P < 0.05). The HK1, HK2, PDHα1 and LDHA mRNA expression in the left ventricle and LDHA mRNA expression were significantly upregulated after 4 weeks MCT injection compared to control rats (all P < 0.05). Moreover, HK1 mRNA expression in the left ventricle was significantly higher in the MCT-PAH-4w group than in MCT-PAH-3w group (P < 0.05). Immunohistochemistry analysis evidenced increasing HK1 positive cells in both left and right ventricle in proportion to MCT injection time and positive HK1 cells were significantly higher in the right ventricle than in left ventricle of MCT-PAH-3w and MCT-PAH-4w rats. Furthermore, the HK1 protein expression in left ventricular tissue form MCT-PAH-4w group and in right ventricular tissue from MCT-PAH-3w and MCT-PAH-4w groups were also significantly upregulated compared to control group (P < 0.05).
Conclusions: Energy metabolic shift occurs both in the left and right ventricles in this PAH model. Upregulated HK1 expression appeares earlier in right ventricle compared to left ventricle. Interference on right ventricular glycolysis may be a potential novel therapy target of PAH.