Escarcega González Carlos E, González Hernández Abimael, Villalón Carlos M, Rodríguez Martin G, Marichal Cancino Bruno A
Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico.
Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.
J Vasc Res. 2018;55(3):159-168. doi: 10.1159/000489956. Epub 2018 Jun 22.
Infantile hemangiomas (IH) are frequent (4-5% of the childhood population) benign vascular tumors that involve accumulation, proliferation, and differentiation of aberrant vascular cells. Typically, IH are innocuous and spontaneously disappear, but they represent a potential risk for harmful effects in the body (e.g., permanent disfigurement) and health (e.g., ulcerations) in some patients. From a serendipitous discovery, the nonselective β-adrenoceptor blocker propranolol (which blocks β1-adrenoceptors, β2-adrenoceptors, and β3-adrenoceptors) emerged as an alternative therapy to treat this pathology and it quickly became a first-line treatment for IH. Nevertheless, its specific mechanisms of action remain thus far unknown. In this respect, several studies have suggested that β1-adrenoceptors and β2-adrenoceptors play a role in proliferative and angiogenic mechanisms. However, current basic research studies suggest that β3-adrenoceptors could be also involved. Notably, β3-adrenoceptors stimulate multiple intracellular pathways related to vascular function (e.g., blood flow, angiogenesis, etc.). This review compiles some lines of evidence suggesting that β3-adrenoceptors may: (1) play a role in the pathophysiology of IH and (2) represent a potential therapeutic target for IH treatment. Hence, clinical evidence is mandatory to decide whether incorporation of β3-adrenoceptor blockers into the therapeutic armamentarium may increase effectiveness in the treatment of IH and other vascular anomalies.
婴儿血管瘤（IH）是常见的（占儿童人口的4-5%）良性血管肿瘤，涉及异常血管细胞的积聚、增殖和分化。通常情况下，婴儿血管瘤无害且会自发消退，但在一些患者中，它们对身体（如永久性毁容）和健康（如溃疡）存在潜在的有害影响风险。偶然发现，非选择性β-肾上腺素能受体阻滞剂普萘洛尔（可阻断β1-肾上腺素能受体、β2-肾上腺素能受体和β3-肾上腺素能受体）成为治疗这种疾病的替代疗法，并迅速成为婴儿血管瘤的一线治疗方法。然而，其具体作用机制至今仍不清楚。在这方面，多项研究表明β1-肾上腺素能受体和β2-肾上腺素能受体在增殖和血管生成机制中起作用。然而，目前的基础研究表明β3-肾上腺素能受体也可能参与其中。值得注意的是，β3-肾上腺素能受体可刺激多种与血管功能相关的细胞内途径（如血流、血管生成等）。本综述汇总了一些证据表明β3-肾上腺素能受体可能：（1）在婴儿血管瘤的病理生理学中起作用；（2）代表婴儿血管瘤治疗的潜在治疗靶点。因此，必须有临床证据来决定将β3-肾上腺素能受体阻滞剂纳入治疗手段是否可提高婴儿血管瘤及其他血管异常的治疗效果。
