Icariin influences cardiac remodeling following myocardial infarction by regulating the CD147/MMP-9 pathway

Abstract

Objective We investigated the protective effect of icariin on myocardial infarction-induced cardiac remodeling. Methods A cardiac remodeling model was constructed by ligating rats' coronary artery. Different icariin and CD147 concentrations were administered in the model group, and echocardiography was used to detect systolic function, screening out ideal experimental concentrations. The ventricular systolic function, myocardial apoptosis rate, and expression of collagen type I (Col I), Col III, CD147, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by hematoxylin-eosin staining, TUNEL assay, and western blot. MMP-9 activity was evaluated by gelatin zymography. Results The expression of Col I, Col III, CD147, and MMP-9 was higher, the expression of TIMP-1 was lower, and the maximal rates of left ventricular pressure rise and fall (+dp/dt_max and -dp/dt_max, respectively) were lower in model than control rats. The expression of CD147, MMP-9, Col I, and Col III was lower, the expression of TIMP-1 was higher, and the +dp/dt_max and -dp/dt_max were higher in the icariin than model group. The apoptosis rate was lower in the icariin and icariin + CD147 groups than control group. Conclusion Icariin attenuated myocardial apoptosis following myocardial infarction by apoptosis rate reduction and CD147/MMP-9 pathway inhibition.

Keywords: CD147/MMP-9 pathway; Myocardial infarction; apoptosis; cardiac remodeling; collagen; icariin.

Figure 1.

(a) Electrocardiograms of rats in the sham and model groups. (b) Hematoxylin–eosin staining of the rats’ heart tissues in different groups. Scale bar = 100 µm.

Figure 2.

Apoptosis rate and expression levels of Bcl-2, Bax, and caspase-3 in rat hearts in different groups. (a) TUNEL staining of rats’ heart tissues in different groups; Scale bar = 200 µm. (b) mRNA expression levels. (c, d) Protein expression levels. *P < 0.05 compared with the control group; #P < 0.05 compared with the model group; ΔP < 0.05 compared with the icariin group. n = 3.

Figure 3.

Expression levels of Col I and Col III of rat hearts in different groups. (a) mRNA expression levels. (b, c) Protein expression levels. *P < 0.05 compared with the control group; #P < 0.05 compared with the model group; ΔP < 0.05 compared with the icariin group. n = 3. Col I, collagen type I; Col III, collagen type III.

Figure 4.

Expression levels of CD147, MMP-9, and TIMP-1 of rat hearts in different groups. (a) mRNA expression levels. (b) Protein expression levels. (d) Activity of MMP-9. *P < 0.05 compared with the control group; #P < 0.05 compared with the model group; ΔP < 0.05 compared with the icariin group. n = 3.