论文部分内容阅读
Objective: Heart failure is a major public health problem and a leading cause of mortalit y in Western countries and is frequently preceded by left ventricular hypertrophy (LVH), which is a major predictor for progressive heart.Paraoxonases (PONs) gene cluster (PC), as lactonases,which exhibit catalytic activities toward lactones and organophosphates, could prevent atherosclerosis through the detoxification of oxidized substrates.However, its role in Cardiac Hypertrophy induced by AngⅡ, whose progress was mainly promoted by ROS, remains unknown.Methods and Results:AngⅡ-induced cardiac hypertrophy mouse model was used to analyze the effect of the PC on cardiac hypertrophy formation (n>10).Firstly, levels of members of the PC were detected in mouse heart.The mRNA and protein level of PON2 and PON3 were upregulated after AngⅡ stimulation for four weeks,and protein level of PON 1 was also upregulated although mRNA of PON 1 couldnt be detected.In the animal level, PC Tg mice had a lower Heart Weight/Body Weight Ratios, smaller left ventricle thickness and cardiomyocyte cross area than control mice four weeks after AngⅡ infusion.Importantly, PC Tg mice exhibited less cardiomyocytes death and lower fetal gene expression level than control mice.Conclusion: Our findings reveal a protective role of the PC in AngⅡ-induced cardiac hypertrophy formation and suggest PONs as promising targets for cardiac hypertrophy prevention.