Donor spontaneous intracerebral hemorrhage is associated with systemic activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and subsequent development of coronary vasculopathy in the heart transplant recipient

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

Research output: Contribution to journalArticle

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Abstract

Background - Matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to play a role in the progression of hemorrhagic stroke. We hypothesized that donor intracerebral hemorrhage (ICH) is associated with activation of the metalloproteinases before transplantation that play a key role in the subsequent development of transplant vasculopathy. 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.

Original languageEnglish (US)
Pages (from-to)1724-1728
Number of pages5
JournalCirculation
Volume108
Issue number14
DOIs
StatePublished - Oct 7 2003
Externally publishedYes

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Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Cerebral Hemorrhage
Tissue Donors
Transplantation
Metalloproteases
Messenger RNA
Matrix Metalloproteinase 17
Matrix Metalloproteinase 20
Fibrosis
Spleen
Lymphocytes
Biopsy
Transplant Recipients
Wounds and Injuries
Heart Transplantation
Allografts
Multivariate Analysis
Stroke
Regression Analysis

Keywords

  • Hemorrhage
  • Metalloproteinases
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Donor spontaneous intracerebral hemorrhage is associated with systemic activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and subsequent development of coronary vasculopathy in the heart transplant recipient. / Yamani, Mohamad H.; Starling, Randall C.; Cook, Daniel J.; Tuzcu, E. Murat; Abdo, Ashraf; Paul, Philip; Powell, Kimerly; Ratliff, Norman B.; Yu, Yang; McCarthy, Patrick M.; Young, James B.

In: Circulation, Vol. 108, No. 14, 07.10.2003, p. 1724-1728.

Research output: Contribution to journalArticle

Yamani, Mohamad H. ; Starling, Randall C. ; Cook, Daniel J. ; Tuzcu, E. Murat ; Abdo, Ashraf ; Paul, Philip ; Powell, Kimerly ; Ratliff, Norman B. ; Yu, Yang ; McCarthy, Patrick M. ; Young, James B. / Donor spontaneous intracerebral hemorrhage is associated with systemic activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and subsequent development of coronary vasculopathy in the heart transplant recipient. In: Circulation. 2003 ; Vol. 108, No. 14. pp. 1724-1728.
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abstract = "Background - Matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to play a role in the progression of hemorrhagic stroke. We hypothesized that donor intracerebral hemorrhage (ICH) is associated with activation of the metalloproteinases before transplantation that play a key role in the subsequent development of transplant vasculopathy. 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.",
keywords = "Hemorrhage, Metalloproteinases, Transplantation",
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T1 - Donor spontaneous intracerebral hemorrhage is associated with systemic activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and subsequent development of coronary vasculopathy in the heart transplant recipient

AU - Yamani, Mohamad H.

AU - Starling, Randall C.

AU - Cook, Daniel J.

AU - Tuzcu, E. Murat

AU - Abdo, Ashraf

AU - Paul, Philip

AU - Powell, Kimerly

AU - Ratliff, Norman B.

AU - Yu, Yang

AU - McCarthy, Patrick M.

AU - Young, James B.

PY - 2003/10/7

Y1 - 2003/10/7

N2 - Background - Matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to play a role in the progression of hemorrhagic stroke. We hypothesized that donor intracerebral hemorrhage (ICH) is associated with activation of the metalloproteinases before transplantation that play a key role in the subsequent development of transplant vasculopathy. 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.

AB - Background - Matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to play a role in the progression of hemorrhagic stroke. We hypothesized that donor intracerebral hemorrhage (ICH) is associated with activation of the metalloproteinases before transplantation that play a key role in the subsequent development of transplant vasculopathy. 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.

KW - Hemorrhage

KW - Metalloproteinases

KW - Transplantation

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