Role of Glucose Regulated Protein 78 in Primary Cardiac Allograft Dysfunction

Purpose Primary graft dysfunction (PGD) refers to the loss of contractility in cardiac allograft within 24 hours after heart transplantation. The mortality among PGD population could be as high as 40% in the modern era. Biological clues for early detection of PGD may ensure prompt management and improvement in patient survival. The applicant proposes in this project that grp78 might be a promising biomarker to predict or to show the severity of PGD in heart transplantation. Methods Clinical variables were collected from patients with and without PGD in National Cheng Kung University from Dec. 2005 to Aug. 2018. The serum levels of grp78 were tested using ELISA. Myocardial tissue expression of endoplasmic reticulum (ER) stress proteins including grp78, hsp70, eIF2α, ATF4 and ATF6 were evaluated using Western blot method. Results A total of 59 patients received heart transplantation in our institution from Dec. 2005 to Aug. 2018. However, not all but 21 patients who meet the inclusion criteria were included in this study. There were 6 patients were suffered from PGD among the 59 heart transplantation patients. The data from another 15 patients were analyzed as the control data. There was significant increase of serum grp78 among patients with PGD, P=0.034. Myocardial tissue expression of grp78 was on the contrary decreased, although this was not statistically significant. There were significantly reduced abundances of eIF2α and increased protein abundances of hsp70 and ATF6. Conclusion This study importantly showed the potential of predicting PGD using serum grp78. Due to the limited case number, we were not able to show a cut-off value of prediction. The future study of mechanism for ER stress in PGD is also important to reveal the potential etiologies.