Matrix metalloproteases and their tissue inhibitor in cardiac transplantation.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Aharinejad
Seyedhossein
S
Department of Cardiothoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. seyedhossein.aharinejad@meduniwien.ac.at
Krenn
Katharina
K
Zuckermann
Andreas
A
Schäfer
Romana
R
Paulus
Patrick
P
Seebacher
Gernot
G
Wolner
Ernst
E
Grimm
Michael
M
D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D011184:Postoperative Period; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D007166:Immunosuppressive Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1