Verteporfin attenuates cardiac fibrosis after myocardial infarction by suppressing the YAP-Smad2/3 signaling pathway

Abstract Purpose Excessive cardiac fibrosis and remodeling occur after myocardial infarction. Yes-associated protein (YAP) is a major transcriptional co-activator of the Hippo pathway and an important regulator of cardiac fibrosis. Verteporfin is a pharmacological inhibitor of YAP that effectively inhibits fibrosis and inflammatory responses. Therefore, this study aimed to explore the effects of verteporfin on cardiac fibrosis after myocardial infarction (MI) and its possible mechanisms. Methods Wild-type C57BL/6J mice were subjected to MI by ligating their left anterior descending coronary artery (LAD) and treating them with verteporfin (50 mg/kg/48 h) or phosphate-buffered saline for 2 weeks. Echocardiography was performed to evaluate cardiac function after 2 weeks, and hematoxylin and eosin and Masson staining were performed to evaluate the degree of myocardial fibrosis and inflammatory response. The protein expression levels of the YAP-Smad2/3 pathway, inflammatory factors, and fibrosis markers in the heart and in vitro were determined using western blotting and immunofluorescence staining. Results Compared to the MI group, verteporfin treatment improved cardiac function and fibrosis in mice post-MI. Moreover, myocardial YAP and SMAD2/3 expression were reduced in verteporfin-treated animals. Hematoxylin and eosin staining and molecular examination showed inflammatory factor and cardiac fibrosis marker expression in the heart sections. Conclusion Verteporfin can attenuate cardiac fibrosis and inflammatory responses and improve cardiac function by suppressing the YAP-Smad2/3 signaling pathway post-MI.