Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (αvβ3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy

Mohamad H. Yamani, E. Murat Tuzcu, Randall C. Starling, Norman B. Ratliff, Yang Yu, D. Geoffrey Vince, Kimerly Powell, Daniel Cook, Patrick McCarthy, James B. Young

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background - Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin αvβ3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. Methods and Results - Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for αvβ3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of αvβ3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0,01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24±1.8% versus 14±1.1%, P<0,001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54±0.1 versus 0.26±0.06 mm; P=0.031). Conclusions - Myocardial ischemic injury after cardiac transplantation is associated with upregulation of αvβ3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.

Original languageEnglish (US)
Pages (from-to)1955-1961
Number of pages7
JournalCirculation
Volume105
Issue number16
DOIs
StatePublished - Apr 23 2002
Externally publishedYes

Fingerprint

Integrin alphaVbeta3
Heart Transplantation
Matrix Metalloproteinases
Thromboplastin
Up-Regulation
Ischemia
Wounds and Injuries
Transplantation
Fibrosis
CD147 Antigens
Tunica Intima
Matrix Metalloproteinase 3
Control Groups
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Integrins
Allografts
Endothelial Cells
Transplants
Biopsy

Keywords

  • Glycoproteins
  • Metalloproteinases
  • Transplantation
  • Ultrasonics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (αvβ3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy. / Yamani, Mohamad H.; Tuzcu, E. Murat; Starling, Randall C.; Ratliff, Norman B.; Yu, Yang; Vince, D. Geoffrey; Powell, Kimerly; Cook, Daniel; McCarthy, Patrick; Young, James B.

In: Circulation, Vol. 105, No. 16, 23.04.2002, p. 1955-1961.

Research output: Contribution to journalArticle

Yamani, Mohamad H. ; Tuzcu, E. Murat ; Starling, Randall C. ; Ratliff, Norman B. ; Yu, Yang ; Vince, D. Geoffrey ; Powell, Kimerly ; Cook, Daniel ; McCarthy, Patrick ; Young, James B. / Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (αvβ3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy. In: Circulation. 2002 ; Vol. 105, No. 16. pp. 1955-1961.
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abstract = "Background - Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin αvβ3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. Methods and Results - Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for αvβ3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of αvβ3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0,01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24±1.8{\%} versus 14±1.1{\%}, P<0,001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54±0.1 versus 0.26±0.06 mm; P=0.031). Conclusions - Myocardial ischemic injury after cardiac transplantation is associated with upregulation of αvβ3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.",
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T1 - Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (αvβ3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy

AU - Yamani, Mohamad H.

AU - Tuzcu, E. Murat

AU - Starling, Randall C.

AU - Ratliff, Norman B.

AU - Yu, Yang

AU - Vince, D. Geoffrey

AU - Powell, Kimerly

AU - Cook, Daniel

AU - McCarthy, Patrick

AU - Young, James B.

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Y1 - 2002/4/23

N2 - Background - Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin αvβ3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. Methods and Results - Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for αvβ3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of αvβ3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0,01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24±1.8% versus 14±1.1%, P<0,001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54±0.1 versus 0.26±0.06 mm; P=0.031). Conclusions - Myocardial ischemic injury after cardiac transplantation is associated with upregulation of αvβ3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.

AB - Background - Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin αvβ3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. Methods and Results - Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for αvβ3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of αvβ3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0,01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24±1.8% versus 14±1.1%, P<0,001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54±0.1 versus 0.26±0.06 mm; P=0.031). Conclusions - Myocardial ischemic injury after cardiac transplantation is associated with upregulation of αvβ3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.

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