The Expression Of Pro-BDNF And Its Receptor In Acute Myocardial Infarction

The expression of Pro-BDNF and its receptor in rat myocardium after acute myocardial infarctionObjective:To investigate the expression profiles of brain-derived neurotrophic factor precursor (proBDNF) and its receptor p75NTR, Sortilin in rat myocardium after acute myocardial infarction (AMI). To discuss the roles of proBDNF and its receptors in the development of AMI.Methods:AMI rat model was established via left anterior descending coronary artery ligation.42 SD(Sprague-Dawley) rats were randomly divided into two groups:the sham group (n=6) and AMI group (n=36). The rats in AMI groups were sacrificed at 1h,6h, Id,3d,7d,14d after AMI (n=6 for each time point) and myocardial specimens were obtained. The expression of proBDNF and its receptors, P75NTR and Sortilin in the infarct area, peri-infarct area and non-infarct area after AMI were determined by immunohistochemistry and Western blot.Results:(1) Immunohistochemical result:In the sham group, proBDNF and its receptors, p75NTR and Sortilin were mildly expressed in the cardiomyocytes and endothelial cells. In AMI group, intensive positive staining of proBDNF and its receptor p75NTR,Sortilin were observed at each time point after surgery in the infarct area. In the non-infarct area, intensive immunoreactivity of proBDNF and Sortilin were observed at 6h,1d after surgery in the non-infarct area. Thereafter, the intensity of staining gradually decreased and comparable to the sham-operated control; however, the e expression of p75NTR was not changed and weakly expressed in the myocardium in the non-infarct. area after AMI. (2) Western Blot:In infarct area in the AMI group, the expression of proBDNF and Sortilin began to increase at 1h after surgery, the upregulation of proBDNF and Sortilin reached peak levels at 6 hours after myocardial infarction. After that, the expression of proBDNF and sortilin declined slightly after 1 day and 3 days after surgery but still higher than that in the sham-operated control. In the peri-infarct and remote area, activation of proBDNF and sortilin was observed at 1 hour after surgery, and the activation became more robust at 6 hours and 1 day after myocardial infarction. Thereafter, the activation was gradually decreased but still higher than the sham-operated control at 14 days after surgery. Similarly, in the infarct area, the expression of P75NTR was dramatically upregulated at 1h,6h after surgery, and still increased at 1day and 3days after surgery, the expression then decreased gradually, at 7 days and 14 days after surgery, the expression of p75NTR was still higher than the sham-operated control. However, in the peri-infarct and remote area, the expression of p75NTR was not changed greatly at each time point after surgery. Conclusion:(1) proBDNF and its receptors, p75NTR and Sortilin are weakly expressed in the cardiomyocytes and endothelial cells in the myocardium. (2) Myocardium infarction induces the activation of proBDNF, p75NTR and Sortilin in the infarct area as well as the peri-infarct area. The activation of proBDNF signaling may be involved in the pathogensis of acute myocardial infarction through inducing cardiomyocyte apoptosis, reducing angiogenesis and the following cardiac remodeling. Further studies are needed to explore the exact roles of proBDNF signaling in the development of AMI and the following cardiac remodeling.