Abstract: OBJECTIVE: To investigate the effect of demethylation of endothelin converting enzyme 1 (ECE-1) gene on left ventricular hypertrophy in rats undergoing abdominal aortic constriction (AAC) and its effect on the PI3K/PKB signaling pathway. METHODS: 30 male SD rats were randomly divided into three groups:control,model and sham groups,with 10 rats in each group. Pressure overload myocardial hypertrophy model was established by AAC in the model group,abdominal aorta was isolated in the sham group but not ligated,and conventional operation was not performed in the control group. Left ventricular end-diastolic diameter (LVED),left ventricular posterior wall thickness (LVPWT),ejection fractions (EF),and fractional shortening (FS) were measured using echocardiography. Heart weight indices (HWI) were calculated after weighing. The areas of myocardial cells (AMC) were measured using hematoxylin-eosin staining. Demethylation levels of ECE-1 genes were detected using methylation-specific PCR. Expressions of atrial natriuretic peptide (ANP) and ECE-1 were detected using Real-time quantitative PCR. Plasma endothelin 1 (ET-1) levels were detected using enzyme-linked immunosorbent assay. Protein expressions of p-PI3K,PI3K,p-PKB and PKB were detected using Western blot. RESULTS: Compared with the control group,there were no statistically significant differences in the indicators of the sham group. Compared with the sham group,LVPWT,HWI,AMC,the demethylation level of ECE-1 gene in ventricular myocardium,plasma ET-1 level,ECE-1 and ANP mRNA in model group were increased (P < 0.01). LVED,EF,FS and the protein expression of p-PI3K and p-PKB in myocardium were decreased (P < 0.01 or P < 0.05). CONCLUSION: ECE-1 gene demethylation is involved in the formation of pressure overload cardiac hypertrophy,which may be related to the inhibition of PI3K/PKB signaling pathway.

Key words: left ventricular hypertrophy, abdominal aortic constriction, gene demethylation, ECE-1, PI3K/PKB signaling pathway