The Observation of Liver and Kidney Injury and the Activation of Macrophages in the Overload Pressure Induced Cardiac Hypertrophy/Heart Failure Mouse Model

  Objective  The purpose of this study is to investigate the injury of liver and kidney tissues in overload pressure induced cardiac hypertrophy/heart failure mice model and the changes of macrophage activation level.

  Methods  6-8 week-old C57BL/6 mice were subjected to transverse aortic constriction (TAC) surgery to establish the cardiac hypertrophy/heart failure mouse model induced by pressure overload, while the aortic was not ligated in the Sham group. At 4 weeks and 8 weeks after TAC, the mice of each group were subjected to echocardiography and blood collection. And mice were sacrificed to collect samples of the heart, liver, and kidney tissues. The contents of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and serum creatinine (Scr) in Sham group and two operation groups were determined. The histological changes of liver, heart and kidney tissues were observed by HE staining, and the expression of the marker of macrophage activation, F4/80 protein, was detected in the heart, liver and kidney tissue by immunohistochemical staining.

  Results  Cardiac hypertrophy occurred at 4 weeks after TAC operation in C57BL/6 mice and developed into heart failure at 8 weeks after TAC. The echocardiography showed that, compared with the Sham group, the left ventricular end-diastolic posterior wall thickness (LVPWd) and the left ventricular internal diameter in diastole (LVIDd) were significantly increased, while the left ventricular ejection fraction (EF) and the left ventricular fractional shortening (FS) were significantly decreased (P<0.05) in the 4-week-TAC group and 8-week-TAC group. The plasma content of ALT, AST, TBil and Scr in the 4-week-TAC group and 8-week-TAC group were significantly higher than those in the Sham group (P<0.05). HE staining showed obvious liver pathological changes in TAC mice, such as vacuolation, mild hepatic sinusoid congestion and inflammatory infiltration in mice post 4 weeks after surgery, and such liver injury was worse in mice post 8 weeks after surgery. Besides, there was a slight damage in renal tissue shown by HE staining, such as slight glomerular injury and slight bleeding. F4/80 protein immunohistochemical staining results demonstrated that the activation of macrophages in the heart and liver in the 4-week-TAC group and 8-week-TAC group was significantly increased than that in the sham group (P<0.05), but there was no significant difference in kidney tissues in groups.

  Conclusion  Macrophages are involved in the process of liver and kidney injury in cardiac hypertrophy/heart failure.