Enhanced ADAM17 expression is associated with cardiac remodeling in rats with acute myocardial infarction

Abstract

AimThis study aimed to investigate the dynamic expression of A-disintegrin-and-metalloproteinase-17 (ADAM17) during cardiac remodeling after acute myocardial infarction (AMI). Main methodsForty male Wistar rats with a permanent ligation of the left anterior descending artery were equally divided into four groups based on predefined sacrifice time: MI1d, MI1w, MI4w and MI12w. As controls, 36 rats only with left thoracotomy were equally divided into four groups. Cardiac remodeling was assessed by echocardiography and hematoxylin and eosin (H&E) staining. ADAM17 mRNA was detected by real-time reverse transcription polymerase chain reaction, and protein expression of ADAM17, tissue inhibitor of metalloproteinases-3 (TIMP-3) and TNF-α was analyzed by western blotting. Key findingsThe systolic function was sharply worsened in the MI1w group (versus the Con1w group, P<0.05), but left ventricular weight index was significantly increased after 4weeks post-MI (P<0.05). H&E staining revealed that one week after AMI, myocardial tissue in the epicardial border zone of the infarcted heart was mixed with broken mitochondrial cristae and decreased matrix density. ADAM17 mRNA and protein expression was significantly increased, accompanied by decreased TIMP-3 and upregulated TNF-α expression in the MI1w group (versus the MI1d group, all P<0.05). Moreover, dynamic ADAM17 mRNA expression was positively correlated with enlarged LVEDd and LVESd (P=0.001, P=0.003) and negatively with LVEF (P=0.039) in AMI rats. SignificanceEnhanced ADAM17 expression, along with decreased TIMP-3 and increased TNF-α expression, especially within one week after AMI, is associated with cardiac remodeling.