VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients

被引:49
作者
Daly, Kevin P. [1 ,2 ,3 ]
Seifert, Michael E. [1 ,3 ]
Chandraker, Anil [3 ,4 ]
Zurakowski, David [3 ,5 ]
Nohria, Anju [3 ,6 ]
Givertz, Michael M. [3 ,6 ]
Karumanchi, S. Ananth [3 ,7 ,8 ]
Briscoe, David M. [1 ,3 ]
机构
[1] Boston Childrens Hosp, Div Nephrol, Dept Med, Transplantat Res Ctr, Boston, MA 02115 USA
[2] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
[4] Brigham & Womens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA
[5] Boston Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA
[6] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA
[7] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA
[8] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA
基金
美国国家卫生研究院;
关键词
heart transplantation; coronary artery disease; angiogenic proteins; biologic markers; ENDOTHELIAL GROWTH-FACTOR; LUNG TRANSPLANTATION; INTERNATIONAL SOCIETY; GENE-EXPRESSION; WORKING FORMULATION; KIDNEY-TRANSPLANTS; CHRONIC REJECTION; IMMUNE-RESPONSE; T-CELLS; HEART;
D O I
10.1016/j.healun.2012.09.030
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: Cardiac allograft vasculopathy (CAV), the major cause of late allograft loss after cardiac transplantation, results from donor-directed cellular and humoral alloimmune responses. Graft vascular endothelial cells (EC) are primary targets of these destructive responses, suggesting that factors associated with endothelial injury and repair could serve as biomarkers of CAV. METHODS: Using a protein profiler array platform, we measured the levels of 55 angiogenesis-related proteins in sera from 33 adult heart transplant recipients, including 17 with angiographically documented CAV and 16 age- and gender-matched controls without CAV. All patients were >2 years after heart transplant. RESULTS: The study population was 75% male with a mean age of 62 +/- 11 years. On average, patients were 12 +/- 5 years after heart transplantation. We found that vascular endothelial growth factor (VEGF)C, VEGF-A, angiopoietin-2, artemin, urokinase-type plasminogen activator and vasohibin were strongly associated with established CAV (all p < 0.01). Multivariable modeling identified VEGF-C, VEGF-A and platelet factor-4 (PF-4) as significant independent biomarkers of CAV. Furthermore, receiver-operating characteristic curve analysis demonstrated that the combination of all 3 molecules provided outstanding performance for the diagnosis of CAV (area under the curve [AUC] = 0.98; p < 0.001). CONCLUSIONS: Serum levels of VEGF-C, VEGF-A and PF-4 demonstrate strong associations with established CAV and, together with related angiogenesis factors, may serve as a reliable, non-invasive diagnostic test for CAV in cardiac transplant recipients. J Heart Lung Transplant 2013;32:120-128 (C) 2013 International Society for Heart and Lung Transplantation. All rights reserved.
引用
收藏
页码:120 / 128
页数:9
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