Effects Of All-trans Retinoic Acid On Pressure Overload Induced Cardiac Hypertrophy In Mice

Objective:To investigate the effects of atRA on pressure overload induced cardiac hypertrophy and myocardial fibrosis.Methods:Eighteen Black male C57 mice were randomly divided into three groups:atRA treatment group,cardiac hypertrophy group and sham operation group.There are six mice in per group.Aortic arch of the mice in atRA treatment group and cardiac hypertrophy group were ligated.Operating procedure of the mice in sham operation group was the same of the above two groups,but no ligating aortic arch.The mice in atRA treatment group and sham operation group were injected 5mg/kg.d atRA via abdominal cavity,the mice in cardiac hypertrophy group were injected 10mg/kg.d corn oil.After six weeks,LVDD,LVSD,IVS, PDW,FS and EF were measured by echocardiography.Cardiac hypertrophy parameter such as BW,HWW and LHWW were measured.The morphology of cardiac myocyte and collagen were observed by Hematoxylin-eosin staining.Real time quantitive RT-PCR was used to detect the expression of FN mRNA,COⅢmRNA and ANF mRNA.Results:(1)Cardiac hypertrophy model was succeed to be established by ligating aortic arch for six weeks.Compared with sham operation group,IVS and LVPW of cardiac hypertrophy group were markedly thicker(all P＜0.05),LVDD and LVSD of cardiac hypertrophy group were markedly bigger(all P＜0.01),as well as EF and FS were significantly lower(all P＜0.01);atRA has no effects on IVS and LVPW of atRA treatment group,compared with cardiac hypertrophy group,there are no statistical significance(P＞0.05);However,atRA can prevent LV dilation and improve heart function,compared with cardiac hypertrophy group,LVDD and LVSD of atRA treatment group were markedly smaller,EF and FS of atRA treatment group were markedly lower(P＜0.05 or P＜0.01).(2)Cardiac weight parameter HWW,LHWW,HWW/BW and LHWW/BW of cardiac hypertrophy group were markedly higher than sham operation group(P＜0.05 or P＜0.01);atRA can not supress cardiac hypertrophy,cardiac weight parameter HWW,LHWW,HWW/BW and LHWW/BW of atRA treatment group were still markedly higher than sham operation group(all P＜0.01),there are no statistical significance between atRA treatment group and cardiac hypertrophy group(P＞0.05);BW of atRA treatment group was lower than the other two groups, compared with sham operation group,the difference was significant(P＜0.05).(3)FN mRNA and COⅢmRNA expression were markedly higher in cardiac hypertrophy group,compared with sham operation group(all P＜0.01);atRA can decrease the expression of FN mRNA and COⅢmRNA in hypertrophic myocardium,compared with cardiac hypertrophy group,there are statistical significance(P＜0.05).(4)The expression of ANF mRNA in cardiac hypertrophy group was were markedly higher than sham operation group(P＜0.01);However,atRA can not decrease the expression of ANF mRNA,compared with cardiac hypertrophy group, there are no statistical significance(P＞0.05).Conclusion:atRA can not prevent cardiac hypertrophy.However,atRA can prevent left ventricular fibrosis and dilation and can improve the EF and FS in pressure overload induced cardiac hypertrophy mice.We find that atRA,a drug used to promote diferentiation,can prevent myocardial fibrosis and cardiovascular remodeling in vivo.This will have far-reaching influence on our understand of the mechanism of cardiovascular remodeling and the development of new anti-remodeling agents.