Efifect Of AMPK?2 Gene Deficiency On Pregnancy-induced Cardiac Hypertrophy

Objective Pregnancy can induce myocardial hypertrophy and cadiac remodeling,but the underlying molecular mechanism is still unclear.AMPK?2 was found to play an important role in protecting heart from pressure overload induced pathological cardiac hypertrophy.Therefore,the purpose of this study was to investigate the role of AMPK?2 in pregnancy induced cardiac hypertrophy by establishing mouse model of pregnancy in AMPK?2 knockout mice and their wild type control mice.Methods AMPK?2 knockout mice and their wild type control mice were divided into wild type control group(WT+NP),wild type with pregnancy group(WT+P),AMPK?2 gene knockout group(KO+NP),AMPK?2 gene knockout with preganancy group(KO+P).Mice echocardiography was applied in four groups to monitor heart function and ventricular mass at three different stages: before and during pregnancy and 2 days after parturition.WGA staining and Sirius red staining were used to observe the change of cardiomyocyte size and myocardial fibrosis separately.Western blotting analysis was performed to determine AMPK pathway related protein expression in myocardial tissue.Results(1)For the left ventricular mass measured by echocardiography in three stages,both WT+P group and KO+P group were shown significantly higher left ventricular mass at the stage of during pregnancy than the other two stages(P<0.01).At the during pregnancy stage,the left ventricular mass weight of WT+P group pregnancy was significantly higher than that of WT+NP group(P<0.01);KO+P group of pregnancy the left ventricular weight was significantly higher than that of KO+NP group(P<0.01);KO+P group of left ventricular weight in pregnancy was significantly higher than that of WT+P group(P<0.05).At the stage of after parturition,the left ventricular mass of group KO+P was significantly higher as compared with KO+NP(P<0.05).(2)Cardiomyocyte cross-sectional area of the WT+P group and KO+P group were significantly higher than their control groups(P<0.01),while KO+P group increased significantly as compared with WT+P group(P<0.01).(3)Compared with WT+NP group,the ratio of ventricular weight/body weight,the ration of left ventricular weight/body weight were found increased significantly in WT+P group(P<0.01);while compared with KO+NP group,the ratio of ventricular weight/body weight,the ratio of left ventricular weight/body weight and the ratio of left ventricular weight/tibial length were all increased significantly KO+P group(P<0.01).The ratio of ventricular weight/body weight,the ratio of left ventricular weight/body weight and the ratio of left ventricular weight/tibial length were all increased significantly in KO+P group as compared with WT+P group(P<0.01).(4)There were no significant difference for myocardial fibrosis in all four groups.(5)AMPK? phosphorylation levels in WT+P group and KO+P group were significantly increased as compared with WT+NP group and KO+NP group separetly(P<0.01),and KO+P group were significantly increased than WT+P group(P<0.01).While the phosphorylation level of ACC in WT+P group and KO+P group were significantly reduced(P<0.01)as compared with WT+NP group and KO+NP group separetly(P<0.01),and KO+P group were significantly decreased than WT+P group(P<0.01).Conclusion(1)Pregnancy could induce adaptive cardiac hypertrophy in both AMPK?2 knock out mice and their wild type control mice with increase of left ventricular mass and cardiomyocyte size,but no myocardial fibrosis.(2)AMPK? gene knockout aggravated the cardiac hypertrophy induced by pregnancy as compared with wild type control mice,which is manifested by the increase of heart weight and the increase of myocardial cell cross-sectional area.(3)Cardiac hypertrophy during pregnancy is closely related to AMPK/ACC signaling pathway.The changes of cardiac adaptation during pregnancy can activate the AMPK signal pathway and play a role in protecting the heart.