Matrix metalloproteases and their tissue inhibitor in cardiac transplantation☆☆☆

Abstract

Multiple studies have shown that matrix metalloproteases (MMPs) are involved in the pathologic reactions occurring as a consequence of cardiac transplantation, including ischemia-reperfusion injury and allograft rejection. This study sought to determine the temporal profile of MMP serum levels following cardiac transplantation. Endomyocardial biopsies and serum samples were obtained from 66 recipients at 1, 2, 3, 4, 7, 12, 24, and 52 weeks post-transplant during the routine follow-up protocol, and MMP-1, MMP-8, MMP-9, and tissue inhibitor of metalloproteases (TIMP)-1 serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Immunosuppression comprised cyclosporine A (CyA; n=46) or tacrolimus (TAC; n=20) with mycophenolate mofetil and steroids. Increased MMP-8, MMP-9, and TIMP-1 serum levels were observed during the first 2 weeks following transplantation compared to the later time points. MMP-1 was increased at 2 and 3 weeks post-transplant compared to all later time points. No correlation of MMP or TIMP serum concentrations with infection episodes was observed. Early increase in MMP and TIMP serum levels following cardiac transplantation indicates involvement of these molecules in the reaction of the transplant to ischemia-reperfusion or early immunologic adaptation processes of the host. Further investigation of the relationship between MMP and TIMP serum levels and clinical conditions following transplantation including allograft rejection and hemodynamic graft function is necessary.