Abstract | BACKGROUND: METHODS AND RESULTS: We evaluated mRNA expressions of MMP-2 and MMP-9 in donor spleen lymphocytes (before transplantation) and in heart biopsies at 1 week after transplantation in 20 recipients from ICH donors and 20 recipients from trauma donors. Patients underwent serial coronary intravascular ultrasound, and interstitial myocardial fibrosis was quantified at 1 year. The baseline characteristics were similar except for increased donor age in the ICH group. Heart biopsies from the ICH group showed significant increased expression of MMP-2 (17-fold, P<0.0001) and MMP-9 (20-fold, P<0.0001) compared with the trauma group. Furthermore, the ICH group showed 1.8-fold (P=0.016) increased mRNA expression of MMP-2 and 1.7-fold (P=0.015) increased mRNA expression of MMP-9 in the donor spleen lymphocytes, suggesting the presence of systemic activation of metalloproteinases before transplantation. At 1 year, the ICH group showed increased myocardial fibrosis and accelerated coronary vasculopathy. Using multivariate regression analysis, MMP-9 was found to be associated with increased risk for vasculopathy independent of donor age (OR, 2.41; P=0.01; 95% CI, 1.24 to 4.69). CONCLUSIONS: This is the first report to describe systemic activation of MMP-2 and MMP-9 in donors with intracerebral hemorrhage and subsequent development of allograft vasculopathy.
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Authors | Mohamad H Yamani, Randall C Starling, Daniel J Cook, E Murat Tuzcu, Ashraf Abdo, Philip Paul, Kimerly Powell, Norman B Ratliff, Yang Yu, Patrick M McCarthy, James B Young |
Journal | Circulation
(Circulation)
Vol. 108
Issue 14
Pg. 1724-8
(Oct 07 2003)
ISSN: 1524-4539 [Electronic] United States |
PMID | 12975253
(Publication Type: Journal Article)
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Chemical References |
- RNA, Messenger
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Adult
- Cerebral Hemorrhage
(complications, enzymology, genetics)
- Coronary Disease
(enzymology, etiology, pathology)
- Coronary Vessels
(diagnostic imaging, pathology)
- Enzyme Activation
- Female
- Heart Transplantation
- Humans
- Male
- Matrix Metalloproteinase 2
(genetics, metabolism)
- Matrix Metalloproteinase 9
(genetics, metabolism)
- Middle Aged
- RNA, Messenger
(metabolism)
- Tissue Donors
- Ultrasonography
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