Early CSWT relieves myocardial fibrosis by inhibiting TGF-Smad2/3-MMP-9

Abstract Objective To investigate the correlation between the improvement of cardiac function and myocardial fibrosis and the TGF-β1-Smad2/3-MMP-9 signaling pathway in acute myocardial infarction (AMI) rats after early treatment with extracorporeal cardiac shock wave therapy (CSWT). Methods Thirty SD rats were randomly divided into five groups: sham group (6 rats), AMI group (6 rats), AMI+CSWT group (6 rats), AMI+SB431542 group (6 rats), and AMI+SB431542+CSWT group (6 rats). AMI was induced in all groups except the sham group. The AMI+CSWT group and AMI+SB431542+CSWT group received CSWT treatment. Echocardiography was performed at 4 days and 62 days postoperatively to assess left ventricular ejection fraction (LVEF) in all groups. Additionally, cardiac tissues were sampled and evaluated for pathological changes and degree of fibrosis by HE staining and Masson staining. The TGF-β1-Smad2/3-MMP-9 signaling pathway and protein expression of COL-I and COL-III were detected in the infarcted border area. Results (1) At 4 days postoperatively, EF and FS were significantly lower, and LVESV was enlarged in the AMI group, AMI+CSWT group, AMI+SB431542+CSWT group, and AMI+SB431542 group compared to the sham group (p < 0.05). (2) At 62 days postoperatively, EF and FS were significantly lower, and LVEDV and LVESV were significantly higher in the AMI group compared to the sham group (p < 0.05). EF and FS were significantly higher, and LVEDV and LVESV were significantly lower in the AMI+CSWT group compared to the AMI group (p < 0.05). There was no significant difference in EF, FS, LVEDV, and LVESV between the AMI+CSWT group and the AMI+SB431542+CSWT group (p > 0.05). (3) Histological analysis showed that the AMI group had more blue-stained areas compared to the sham group, while the AMI+CSWT group had fewer blue-stained areas and more neatly arranged red areas compared to the AMI group (p < 0.05). (4) Collagen volume fraction (CVF) was significantly higher in the AMI group compared to the sham group (p < 0.05). CVF was significantly lower in the AMI+CSWT group compared to the AMI group (p < 0.05). There was no significant difference in CVF between the AMI+CSWT group and the AMI+SB431542+CSWT group (p > 0.05). (5) The expression levels of TGF-β1, Smad3, MMP-9, COL-I, and COL-III were significantly higher in the AMI group compared to the sham group (p < 0.05). The expression levels of these proteins were significantly reduced in the AMI+CSWT group compared to the AMI group (p < 0.05). Conclusions Early CSWT improves cardiac function and inhibits myocardial fibrosis associated with the TGF-β1-Smad2/3-MMP-9 signaling pathway.pathological changesdegree of fibrosis