The Experts below are selected from a list of 2997 Experts worldwide ranked by ideXlab platform
Holger Zimmermann - One of the best experts on this subject based on the ideXlab platform.
-
integrin αvβ3 Vitronectin Receptor is a candidate Receptor for the virulent echovirus 9 strain barty
Journal of General Virology, 1999Co-Authors: Birgit Nelsensalz, Hans J Eggers, Holger ZimmermannAbstract:The enterovirus echovirus 9 strain Barty (E9/Barty) is pathogenic for newborn mice as well as for humans. In contrast to the apathogenic prototype strain Hill, strain Barty encodes an RGD motif in the C-terminal part of the structural protein VP1. Data are presented that show that E9/Barty binds its target cells via contact of the RGD motif to the αvβ3 integrin (Vitronectin Receptor), whereas prototype Hill uses a different, still unidentified Receptor site. Furthermore, virus titres of murine muscle tissue were compared after infection of newborn and 1-, 2-, 3- and 12-week-old mice. The replication capacity of the virus decreased dramatically with age of the infected mice. Since E9/Barty does not replicate or replicates only poorly in mice older than about 5 days, and expression of the Vitronectin Receptor is reported to be down-regulated in striated muscle tissue during development, it is suggested that susceptibility of mice to this echovirus infection is controlled by the availability of αvβ3 integrin.
-
Integrin alpha(v)beta3 (Vitronectin Receptor) is a candidate Receptor for the virulent echovirus 9 strain Barty.
The Journal of general virology, 1999Co-Authors: Birgit Nelsen-salz, Hans J Eggers, Holger ZimmermannAbstract:The enterovirus echovirus 9 strain Barty (E9/Barty) is pathogenic for newborn mice as well as for humans. In contrast to the apathogenic prototype strain Hill, strain Barty encodes an RGD motif in the C-terminal part of the structural protein VP1. Data are presented that show that E9/Barty binds its target cells via contact of the RGD motif to the alpha(v)beta3 integrin (Vitronectin Receptor), whereas prototype Hill uses a different, still unidentified Receptor site. Furthermore, virus titres of murine muscle tissue were compared after infection of newborn and 1-, 2-, 3- and 12-week-old mice. The replication capacity of the virus decreased dramatically with age of the infected mice. Since E9/Barty does not replicate or replicates only poorly in mice older than about 5 days, and expression of the Vitronectin Receptor is reported to be down-regulated in striated muscle tissue during development, it is suggested that susceptibility of mice to this echovirus infection is controlled by the availability of alpha(v)beta3 integrin.
James B. Young - One of the best experts on this subject based on the ideXlab platform.
-
acute vascular rejection is associated with up regulation of Vitronectin Receptor αvβ3 increased expression of tissue factor and activation of the extracellular matrix metalloproteinase induction system
Journal of Heart and Lung Transplantation, 2002Co-Authors: Mohamad H. Yamani, Randall C. Starling, Patrick M. Mccarthy, James B. Young, Daniel J. Cook, Geoffrey D Vince, Norman B. RatliffAbstract:Abstract Background A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of Vitronectin Receptor (αvβ3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. Methods Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for αvβ3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). Results Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of αvβ3 (1.9-fold, p p p Conclusions Acute vascular rejection is associated with up-regulation of αvβ3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, E. Murat Tuzcu, D. Geoffrey Vince, Kimerly A. Powell, Daniel J. Cook, James B. YoungAbstract: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
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, Kimerly A. Powell, Daniel J. Cook, Murat E Tuzcu, Geoffrey D Vince, James B. YoungAbstract: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...
-
Acute cellular rejection following human heart transplantation is associated with increased expression of Vitronectin Receptor (integrin αvβ3)
American Journal of Transplantation, 2002Co-Authors: Mohamad H. Yamani, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, Randall C. Starling, Patrick M. Mccarthy, James B. YoungAbstract:The Vitronectin Receptor (integrin αvβ3), a cell-surface adhesion Receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of αvβ3. We also determined whether fibronectin Receptor (α5β1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute cellular rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.
-
The role of Vitronectin Receptor (αvβ3) and tissue factor in the pathogenesis of transplant coronary vasculopathy
Journal of the American College of Cardiology, 2002Co-Authors: Mohamad H. Yamani, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, Randall C. Starling, Patrick M. Mccarthy, E. Murat Tuzcu, James B. YoungAbstract:Abstract Objectives This study was undertaken to test the hypothesis that transplant coronary vasculopathy (CV) is associated with increased myocardial protein expression of both tissue factor (TF) and integrin αvβ3. Background The Vitronectin Receptor (integrin αvβ3) and TF have recently been found to play a key role in apoptotic cell death and vascular endothelial cell injury. Methods A total of 77 heart transplant recipients underwent simultaneous endomyocardial biopsy and intravascular ultrasound (IVUS) at one year of transplant. Patients with pre-existing donor coronary atherosclerosis (n = 35) or with acute rejection (grade >1A, n = 10) at the time of the IVUS were excluded from the analysis. The remaining 32 patients constitute the cohort of the present study. A computerized biopsy score was derived based on the duration and severity of cellular rejection. Both TF and αvβ3 expression in the heart biopsy specimens were evaluated by immunoperoxidase histochemistry and Western blot analysis. Results Patients with CV (n = 24) had increased expression of αvβ3 (2.7-fold, p = 0.003) and TF (7.9-fold, p = 0.04) compared with patients without evidence of vasculopathy (n = 8). In the absence of myocardial fibrosis, αvβ3 expression correlated significantly with the cellular rejection score (r = 0.58, p = 0.02). Conclusions Transplant vasculopathy is associated with increased expression of both TF and αvβ3. The significant correlation of αvβ3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy.
Mohamad H. Yamani - One of the best experts on this subject based on the ideXlab platform.
-
Quilty lesions are associated with increased expression of Vitronectin Receptor (αvβ3) and subsequent development of coronary vasculopathy
The Journal of Heart and Lung Transplantation, 2003Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, E. Murat Tuzcu, Daniel J. Cook, Timothy Crow, Robert E. Hobbs, Gustavo Rincon, Corinne Bott-silvermanAbstract:Abstract Background: Quilty lesions are common after heart transplantation; however, their relationship to vasculopathy has not been described. We tested the hypothesis that Quilty lesions are associated with increased expression of Vitronectin Receptor (αvβ3) and the subsequent development of coronary vasculopathy. Methods: A total of 140 heart transplant recipients underwent coronary intravascular ultrasound at baseline and at 1 year after transplantation, and we measured the change in coronary maximal intimal thickness. Endomyocardial biopsy specimens taken within 8 weeks after transplantation showed Quilty lesions in 54 of 140 (39%) patients (Quilty group). We compared these results with the remaining 86 of 140 patients (61%) who had no evidence of Quilty lesions during the same period (control group). We evaluated 10 endomyocardial biopsy specimens from each group for αvβ3, using immunohistochemistry staining and immunoblotting. Results: Quilty lesions stained positive for αvβ3, and Western blot analysis showed a 1.3-fold ( p = 0.004) increase in expression of αvβ3. Compared with control, the Quilty group tended to have a greater incidence of post-transplant ischemic injury complicated by fibrosis (54% vs 38%, p = 0.08) and a greater reported incidence of "previous biopsy site" during the first 4 weeks after transplantation (48% vs 32%, p = 0.06). At 1 year, the Quilty group had a significant increase in the change in coronary maximal intimal thickness seen with intravascular ultrasound (0.54 ± 0.34 vs 0.42 ± 0.28 mm, p = 0.038). Conclusions: This is the first report to describe the association of Quilty lesions with coronary vasculopathy and its association with increased αvβ3 expression.
-
acute vascular rejection is associated with up regulation of Vitronectin Receptor αvβ3 increased expression of tissue factor and activation of the extracellular matrix metalloproteinase induction system
Journal of Heart and Lung Transplantation, 2002Co-Authors: Mohamad H. Yamani, Randall C. Starling, Patrick M. Mccarthy, James B. Young, Daniel J. Cook, Geoffrey D Vince, Norman B. RatliffAbstract:Abstract Background A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of Vitronectin Receptor (αvβ3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. Methods Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for αvβ3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). Results Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of αvβ3 (1.9-fold, p p p Conclusions Acute vascular rejection is associated with up-regulation of αvβ3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, E. Murat Tuzcu, D. Geoffrey Vince, Kimerly A. Powell, Daniel J. Cook, James B. YoungAbstract: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
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, Kimerly A. Powell, Daniel J. Cook, Murat E Tuzcu, Geoffrey D Vince, James B. YoungAbstract: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...
-
Acute cellular rejection following human heart transplantation is associated with increased expression of Vitronectin Receptor (integrin αvβ3)
American Journal of Transplantation, 2002Co-Authors: Mohamad H. Yamani, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, Randall C. Starling, Patrick M. Mccarthy, James B. YoungAbstract:The Vitronectin Receptor (integrin αvβ3), a cell-surface adhesion Receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of αvβ3. We also determined whether fibronectin Receptor (α5β1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute cellular rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.
Norman B. Ratliff - One of the best experts on this subject based on the ideXlab platform.
-
Quilty lesions are associated with increased expression of Vitronectin Receptor (αvβ3) and subsequent development of coronary vasculopathy
The Journal of Heart and Lung Transplantation, 2003Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, E. Murat Tuzcu, Daniel J. Cook, Timothy Crow, Robert E. Hobbs, Gustavo Rincon, Corinne Bott-silvermanAbstract:Abstract Background: Quilty lesions are common after heart transplantation; however, their relationship to vasculopathy has not been described. We tested the hypothesis that Quilty lesions are associated with increased expression of Vitronectin Receptor (αvβ3) and the subsequent development of coronary vasculopathy. Methods: A total of 140 heart transplant recipients underwent coronary intravascular ultrasound at baseline and at 1 year after transplantation, and we measured the change in coronary maximal intimal thickness. Endomyocardial biopsy specimens taken within 8 weeks after transplantation showed Quilty lesions in 54 of 140 (39%) patients (Quilty group). We compared these results with the remaining 86 of 140 patients (61%) who had no evidence of Quilty lesions during the same period (control group). We evaluated 10 endomyocardial biopsy specimens from each group for αvβ3, using immunohistochemistry staining and immunoblotting. Results: Quilty lesions stained positive for αvβ3, and Western blot analysis showed a 1.3-fold ( p = 0.004) increase in expression of αvβ3. Compared with control, the Quilty group tended to have a greater incidence of post-transplant ischemic injury complicated by fibrosis (54% vs 38%, p = 0.08) and a greater reported incidence of "previous biopsy site" during the first 4 weeks after transplantation (48% vs 32%, p = 0.06). At 1 year, the Quilty group had a significant increase in the change in coronary maximal intimal thickness seen with intravascular ultrasound (0.54 ± 0.34 vs 0.42 ± 0.28 mm, p = 0.038). Conclusions: This is the first report to describe the association of Quilty lesions with coronary vasculopathy and its association with increased αvβ3 expression.
-
acute vascular rejection is associated with up regulation of Vitronectin Receptor αvβ3 increased expression of tissue factor and activation of the extracellular matrix metalloproteinase induction system
Journal of Heart and Lung Transplantation, 2002Co-Authors: Mohamad H. Yamani, Randall C. Starling, Patrick M. Mccarthy, James B. Young, Daniel J. Cook, Geoffrey D Vince, Norman B. RatliffAbstract:Abstract Background A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of Vitronectin Receptor (αvβ3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. Methods Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for αvβ3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). Results Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of αvβ3 (1.9-fold, p p p Conclusions Acute vascular rejection is associated with up-regulation of αvβ3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, E. Murat Tuzcu, D. Geoffrey Vince, Kimerly A. Powell, Daniel J. Cook, James B. YoungAbstract: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
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, Kimerly A. Powell, Daniel J. Cook, Murat E Tuzcu, Geoffrey D Vince, James B. YoungAbstract: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...
-
Acute cellular rejection following human heart transplantation is associated with increased expression of Vitronectin Receptor (integrin αvβ3)
American Journal of Transplantation, 2002Co-Authors: Mohamad H. Yamani, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, Randall C. Starling, Patrick M. Mccarthy, James B. YoungAbstract:The Vitronectin Receptor (integrin αvβ3), a cell-surface adhesion Receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of αvβ3. We also determined whether fibronectin Receptor (α5β1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute cellular rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.
Randall C. Starling - One of the best experts on this subject based on the ideXlab platform.
-
Quilty lesions are associated with increased expression of Vitronectin Receptor (αvβ3) and subsequent development of coronary vasculopathy
The Journal of Heart and Lung Transplantation, 2003Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, E. Murat Tuzcu, Daniel J. Cook, Timothy Crow, Robert E. Hobbs, Gustavo Rincon, Corinne Bott-silvermanAbstract:Abstract Background: Quilty lesions are common after heart transplantation; however, their relationship to vasculopathy has not been described. We tested the hypothesis that Quilty lesions are associated with increased expression of Vitronectin Receptor (αvβ3) and the subsequent development of coronary vasculopathy. Methods: A total of 140 heart transplant recipients underwent coronary intravascular ultrasound at baseline and at 1 year after transplantation, and we measured the change in coronary maximal intimal thickness. Endomyocardial biopsy specimens taken within 8 weeks after transplantation showed Quilty lesions in 54 of 140 (39%) patients (Quilty group). We compared these results with the remaining 86 of 140 patients (61%) who had no evidence of Quilty lesions during the same period (control group). We evaluated 10 endomyocardial biopsy specimens from each group for αvβ3, using immunohistochemistry staining and immunoblotting. Results: Quilty lesions stained positive for αvβ3, and Western blot analysis showed a 1.3-fold ( p = 0.004) increase in expression of αvβ3. Compared with control, the Quilty group tended to have a greater incidence of post-transplant ischemic injury complicated by fibrosis (54% vs 38%, p = 0.08) and a greater reported incidence of "previous biopsy site" during the first 4 weeks after transplantation (48% vs 32%, p = 0.06). At 1 year, the Quilty group had a significant increase in the change in coronary maximal intimal thickness seen with intravascular ultrasound (0.54 ± 0.34 vs 0.42 ± 0.28 mm, p = 0.038). Conclusions: This is the first report to describe the association of Quilty lesions with coronary vasculopathy and its association with increased αvβ3 expression.
-
acute vascular rejection is associated with up regulation of Vitronectin Receptor αvβ3 increased expression of tissue factor and activation of the extracellular matrix metalloproteinase induction system
Journal of Heart and Lung Transplantation, 2002Co-Authors: Mohamad H. Yamani, Randall C. Starling, Patrick M. Mccarthy, James B. Young, Daniel J. Cook, Geoffrey D Vince, Norman B. RatliffAbstract:Abstract Background A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of Vitronectin Receptor (αvβ3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. Methods Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for αvβ3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). Results Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of αvβ3 (1.9-fold, p p p Conclusions Acute vascular rejection is associated with up-regulation of αvβ3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, E. Murat Tuzcu, D. Geoffrey Vince, Kimerly A. Powell, Daniel J. Cook, James B. YoungAbstract: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
-
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
Circulation, 2002Co-Authors: Mohamad H. Yamani, Norman B. Ratliff, Randall C. Starling, Patrick M. Mccarthy, Kimerly A. Powell, Daniel J. Cook, Murat E Tuzcu, Geoffrey D Vince, James B. YoungAbstract: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...
-
Acute cellular rejection following human heart transplantation is associated with increased expression of Vitronectin Receptor (integrin αvβ3)
American Journal of Transplantation, 2002Co-Authors: Mohamad H. Yamani, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, Randall C. Starling, Patrick M. Mccarthy, James B. YoungAbstract:The Vitronectin Receptor (integrin αvβ3), a cell-surface adhesion Receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of αvβ3. We also determined whether fibronectin Receptor (α5β1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute cellular rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.
