Screening And Differences For Glycolytic Metabolism Related Genes Between Two Ventricles In Pulmonary Arterial Hypertension Rats

Background: Pulmonary arterial hypertension (PAH) is a multifactorial andprogressive disease, which is characterized by a sustained increase in pulmonaryvascular resistance, eventually leading to right heart failure and death. Although thereis many new available therapies at present, PAH remains an incurable disease process.Studies in animal models and human RVH suggest that there is reduced glucoseoxidation and increased glycolysis from the right ventricle hypertrophy to rightventricular failure in the process of PAH rats.Objective: To investigate the differences of cardiac energy metabolism betweenleft and right ventricle in the monocmtaline (MCT) induced pulmonary arterialhypertension(PAH) rats in our study.Methods: PAH was induced by a single subcutaneous injection of MCT (50mg/kg) in rats, who developed right heart failure eventually. At the same time, controlgroup was injected with normal saline. MCT-PAH rats were randomly divided intothree groups according to the treatment of MCT: MCT-2week、3week、4week group(MCT-2w、3w、4w). At the end of study, the hemodynamics and right ventricularhypertrophy were compared in each group. The expression levels of proliferating cellnuclear antigen (PCNA) and TdT-mediated dUTP nick end labeling (TUNEL) weredetected between left and right ventricular myocardial cells. The differences of genesexpression from the glycolytic key candidate genes were screened between twoventricles.Results: After MCT injection for three weeks, mean pulmonary arterialpressure, right ventricular systolic pressure and right ventricular hypertrophy index were significantly increased. The morphology and structure were changed obviouslyin left and right ventricular myocardial cells. Proliferation and apoptotic resistance ofmyocardial cells were markedly increased compared with control group. Theexpression of HK1mRNA began to rise in right ventricle of MCT-3w group, whichwas obviously earlier than left ventricle (MCT-4w group). In the MCT-4w group, theexpression of HK2(hexokinase2)、PDHα1(pyruvate dehydrogenase complex α1)、LDHA (lactate dehydrogenase A) mRNA was significantly increased in left ventricle,while the expression of LDHA only were up-regulated in right ventricle. The HK1mRNA expression was further confirmed by the expression of HK1protein andimmunohistochemistry analysis.Conclusions: Energy metabolic shift occurred in the left and right ventricles inPAH. Up-regulated expression of HK1appeared earlier in right ventricle than leftventricle. Interference of glycolysis of right ventricle may be a novel target of PAH inthe future.