Abstract

Vascular endothelial growth factor-A (VEGF-A) is a master regulator of angiogenesis, with higher levels in infantile hemangioma (IH). The effects of propranolol on IH are not fully understood and may involve vasoconstriction, angiogenesis inhibition, and apoptosis induction. Therefore, we examined the effects of propranolol therapy on levels of VEGF-A in patients with IH in the proliferative phase and compared the VEGF-A levels to those in untreated patients in the involuting or involuted phases, as well as studied the consistency between the clinical and VEGF responses in patients receiving treatment. In a prospective study, we compared 24 patients with IH in the proliferative phase to 9 patients with IH in the involuting or involuted phase, assessing clinical responses to therapy and changes in VEGF-A levels after 3 months. The median VEGF level before treatment was 275 pg/ml; however, after 3 months, the level significantly decreased to 100 pg/ml (P = 0.007). Median VEGF was significantly higher in patients in the proliferative phase after 3 months of treatment (100 pg/ml) as compared to those in the involuting phase (50 pg/ml). We found no significant correlation between VEGF level and IH size reduction. Propranolol therapy induced a significant decline in VEGF levels at the 3-month evaluation in patients in the proliferative phase; however, this did not reach the levels of IH in the involuting phase. VEGF response was not translated to a clinical response in some patients with IH. These results put in uncertainty the clinical benefit of targeting VEGF pathway in IH.

摘要

血管内皮生长因子-A (VEGF-A) 是血管生成的主要调节因子，在婴儿血管瘤 (IH) 中含量较高。普萘洛尔对 IH 的影响尚不完全清楚，可能涉及血管收缩、血管生成抑制和细胞凋亡诱导。因此，我们检查了普萘洛尔治疗对增殖期 IH 患者 VEGF-A 水平的影响，并将 VEGF-A 水平与消退期或消退期未治疗患者的 VEGF-A 水平进行了比较，并研究了两者之间的一致性。接受治疗的患者的临床和 VEGF 反应。在一项前瞻性研究中，我们比较了 24 名处于增殖期的 IH 患者与 9 名处于消退期或消退期的 IH 患者，评估了治疗的临床反应和 3 个月后 VEGF-A 水平的变化。治疗前的中位 VEGF 水平为 275 pg/ml；然而，3 个月后，水平显着下降至 100 pg/ml（P  = 0.007)。与消退期患者（50 pg/ml）相比，治疗 3 个月后增殖期患者（100 pg/ml）的中位 VEGF 显着更高。我们发现 VEGF 水平与 IH 大小减少之间没有显着相关性。在增殖期患者的 3 个月评估中，普萘洛尔治疗导致 VEGF 水平显着下降；然而，这并没有达到渐消期的IH水平。在一些 IH 患者中，VEGF 反应没有转化为临床反应。这些结果不确定在 IH 中靶向 VEGF 途径的临床益处。