Expression of membrane-type 1 matrix metalloproteinase in coronary vesselsof allotransplanted primate hearts

Citation
K. Tsukioka et al., Expression of membrane-type 1 matrix metalloproteinase in coronary vesselsof allotransplanted primate hearts, J HEART LUN, 19(12), 2000, pp. 1193-1198
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
JOURNAL OF HEART AND LUNG TRANSPLANTATION
ISSN journal
1053-2498 → ACNP
Volume
19
Issue
12
Year of publication
2000
Pages
1193 - 1198
Database
ISI
SICI code
1053-2498(200012)19:12<1193:EOM1MM>2.0.ZU;2-1
Abstract
Background: The mechanisms of intimal thickening in cardiac allograft vascu lopathy (CAV) remain controversial after heart transplantation Matrix metal loproteinase-2 (MMP-2) plays a crucial role in degrading extracellular matr ix (ECM) during neointimal formation. Recently, it has been revealed that M MP-2 is activated by membrane-type 1 matrix metalloproteinase (MT1-MMP). Th is process involves tissue inhibitor of MMP-2 (TIMP-2), forming an MT1-MMP/ TIMP-2/pro-MMP-2 complex. In this study, we hypothesize that these componen ts contribute to the pathogenesis of CAV. Methods: Heterotopic cardiac allografting was performed in randomly paired Japanese monkeys with an immunosuppressive regimen of intravenous administr ation of antihuman CD18 monoclonal antibody. The donor hearts were harveste d at Days 22, 28, 40, 41, and 95 posttransplantation. We examined expressio n of MMP-2, MT1-MMP, and TIMP-2 of graft vessels using immunohistochemistry and protein level by western blot analysis. Results: Pathologically, various degrees of neointimal formation were obser ved. In the allografts harvested at Days 22, 28, 40, and 41, MT1-MMP was ex pressed in the endothelial cells and smooth muscle cells (SMCs) in media of some arteries without histological change, accompanied by expression of MM P-2 and TIMP-2. In the severely thickened neointima of the allograft harves ted at Day 95, MMP-2 and faint MT1-MMP were expressed in SMCs of severely t hickened neointima and media; TIMP-2 expression was seen only in noncollage nous tissue of severely thickened neointima. MMP-2 protein was more intense ly expressed in the allograft harvested at Day 95 than in the allograft har vest at Day 41, while TIMP-2 protein level was almost same in the 2 samples . Conclusion: We observed the simultaneous expression of MMP-5 MT1-MMP, and T IMP-2. Thus, ECM degradation triggered by MT1-MMP/TIMP-2/pro-MMP-2 complex could be a novel mechanism of CAV.