BACKGROUND Vascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. METHODS We examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into 3 equal-sized groups (low VEGF <500 ng/liter, n = 28; moderate VEGF 500-3000 ng/liter, n = 28; and high VEGF >3000 ng/liter, n = 27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for 5 years. RESULTS Baseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. CONCLUSIONS Our findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria.

中文翻译：

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供体血浆 VEGF-A 作为心脏移植后心肌损伤和原发性移植物功能障碍的生物标志物。


背景血管内皮生长因子(VEGF)-A是一种血管生成和促炎细胞因子，对微血管通透性和血管舒张具有深远影响。有几个过程可能会诱导脑死亡器官捐献者中 VEGF-A 的表达。然而，目前尚不清楚供体 VEGF-A 是否与心脏移植后的不良后果有关。方法 我们检查了 83 名心脏移植捐献者的血浆 VEGF-A 水平以及这些捐献者及其各自在 2010 年至 2016 年间接受手术的接受者的临床数据。使用基于 Luminex 的 Multiplex 分析捐献者血浆，并通过单靶点 ELISA 进行确认。根据供体 VEGF-A 血浆水平，受者被分为 3 个同等大小的组（低 VEGF <500 ng/L，n = 28；中度 VEGF 500-3000 ng/L，n = 28；高 VEGF >3000纳克/升，n = 27)。对心肌损伤以及心脏移植和肾功能的生化和临床参数进行了一年的随访，同时对排斥反应、心脏同种异体移植血管病变的发生和死亡率进行了五年的监测。结果 供者组之间的基线参数具有可比性，但年龄除外，低、中和高供者血浆 VEGF 水平组的中位年龄分别为 40、45 和 50 岁，因此供者年龄被列为混杂因素。因素。高供体血浆 VEGF-A 水平与心脏移植后受者明显的心肌损伤（TnT 和 TnI）、较高的正性肌力评分以及较高的原发性移植物功能障碍发生率相关。 此外，接受来自血浆 VEGF-A 水平高的供体的同种异体移植物的受者在重症监护室和医院的停留时间更长，并且延长肾脏替代治疗的可能性增加。结论 我们的研究结果表明，供体血浆 VEGF-A 水平升高与心脏移植受者的不良结局相关，特别是在心肌损伤、原发性移植物功能障碍和长期肾脏并发症方面。供体 VEGF-A 可以作为潜在的生物标志物，用于预测这些不良结果并确定扩展的供体标准。