Department of Health Science, Dermatologic Division, Meyer Children Hospital, Florence, Italy.
Division of Pathology, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
Pediatr Res. 2022 Jan;91(1):163-170. doi: 10.1038/s41390-021-01385-x. Epub 2021 Mar 2.
Propranolol (antagonist of β-/β-AR but minimally active against β-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of β-AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of β-ARs, we evaluated a possible relationship between β-AR expression and response to propranolol.
Fifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of β-, β-, and β-ARs positively stained area was compared between the two groups.
While no difference was found in both β- and β-AR expression level, a statistically significant increase of β-AR positively stained area was observed in the nonresponder group.
Although the number of biopsies is insufficient to draw definitive conclusions, and the different β-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between β-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH.
Propranolol (unselective antagonist of β and β-ARs) is currently the first-line treatment for IHs, with a success rate of ~60%. Its effectiveness has been attributed to its ability to block β-ARs. However, β-ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol. This study suggests a possible role of β-ARs in hemangioma pathogenesis and a possible new therapeutic target.
普萘洛尔（β-/β-AR 拮抗剂，但对 β-AR 的活性较低）目前是婴幼儿血管瘤（IH）的一线治疗药物。其疗效归因于β-AR 的阻断。然而，其成功率约为 60%。鉴于人们对β-AR 在血管生成中的作用越来越感兴趣，我们评估了β-AR 表达与普萘洛尔反应之间的可能关系。
从 IH 患者的外科活检样本中采集了 15 个样本。其中 3 个取自婴儿早期，随后成功用普萘洛尔治疗（应答组）。其余 12 个取自对普萘洛尔反应不完全的残留病变（无应答组）。比较两组中β-、β-和β-AR 阳性染色面积的百分比的形态计量学分析。
两组β-和β-AR 表达水平无差异，但无应答组β-AR 阳性染色面积明显增加。
尽管活检数量不足以得出明确的结论，并且不同的β-AR 模式可能可以通过不同的采样时间来理论解释，但这项研究表明β-AR 表达与普萘洛尔治疗反应降低之间可能存在相关性。这项研究为管理 IH 开辟了新的治疗前景。
普萘洛尔（β 和β-AR 的非选择性拮抗剂）目前是 IH 的一线治疗药物，成功率约为 60%。其有效性归因于其阻断β-AR 的能力。然而，在对普萘洛尔无反应的患者的血管瘤活检中，β-AR （普萘洛尔对其活性较低）的表达明显更高。这项研究表明β-AR 可能在血管瘤发病机制中起作用，并可能成为新的治疗靶点。
