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

VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients.
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DOI:
10.1016/j.healun.2012.09.030
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发表时间:
2013-01
期刊:
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子:
--
通讯作者:
Briscoe DM
Briscoe DM
中科院分区:
其他
文献类型:
--
作者:
Daly KP;Seifert ME;Chandraker A;Zurakowski D;Nohria A;Givertz MM;Karumanchi SA;Briscoe DM

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心脏移植物血管病(cardiac allograft vasculopathy,CAV)是心脏移植术后晚期移植物失功的主要原因,由供者介导的细胞和体液免疫反应引起。移植物血管内皮细胞(EC)是这些破坏性反应的主要靶点,这表明与内皮损伤和修复相关的因子可以作为CAV的生物标志物。使用蛋白质分析仪阵列平台,我们测量了33名成人心脏移植受者血清中55种血管生成相关蛋白的水平,其中包括17名血管造影记录的CAV和16名年龄和性别匹配的无CAV对照。所有患者均为心脏移植后2年以上。研究人群中75%为男性,平均年龄为62 ± 11岁。平均而言,患者在心脏移植后12 ± 5年。我们发现血管内皮生长因子(VEGF)-C、VEGF-A、血管生成素-2、artemin、尿激酶型纤溶酶原激活剂和血管抑制素与确诊的CAV密切相关(均p < 0.01)。多变量模型确定VEGF-C、VEGF-A和血小板因子-4(PF-4)是CAV的重要独立生物标志物。此外,受试者操作特征曲线分析表明,所有3种分子的组合为诊断CAV提供了出色的性能(曲线下面积[AUC] = 0.98; p < 0.001)。血清VEGF-C、VEGF-A和PF-4水平与已建立的CAV有很强的相关性,与相关的血管生成因子一起,可作为心脏移植受者CAV的可靠、非侵入性诊断试验。
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. 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. 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). 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.
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