Mechanism of Action of β-blockers on Infantile Hemangiomas
The exact mechanism of action of β-blockers for the treatment of IH is not yet completely understood, however, it is postulated to inhibit growth by at least four distinct mechanisms: vasoconstriction, inhibition of angiogenesis or vasculogenesis, induction of apoptosis, and recruitment of endothelial progenitor cells (EPCs) to the site of the hemangioma.[18–21] Of note, β-adrenergic receptors are expressed on endothelial cells of IH, which are found in abundance in the proliferative phase of IH.
Vascular tone results from a complex interplay of a variety of chemokines in the body and their interaction with receptors located on endothelial cell surfaces. Several studies have demonstrated that activation of β-adrenergic receptors promotes vasodilation.[19,22] The use of β-blockers to mitigate the interaction of adrenaline mediated activation of β2-receptors results in vasoconstriction, which leads to reduced blood flow within the hemangioma. Clinically, propranolol can induce a noticeable change in color, as well as softening of the IH, often within the first few days or even hours after initiating therapy.
Activation of β-adrenergic receptors leads to increased release of VEGF, which appears to promote both angiogenesis and vasculogenesis in IH. Inhibition of these receptors by β-blockers results in reduced VEGF production, thereby limiting proliferation of vasculature and possibly arresting growth.
β-adrenergic receptors are thought to play a role in apoptosis. Blockade of β-receptors have been shown to induce apoptosis in cultured endothelial cells, which is hypothesized to contribute to the effectiveness of propranolol in the treatment of IH. In addition, newer literature also reports that beta blockage can also promote involution of IH through regulation of the renin-angiotensin pathway. As well, β-blockers may decrease migration of EPCs, such that they are prevented from migrating to areas predisposed to hemangioma formation.
Skin Therapy Letter. 2013;18(6) © 2013 SkinCareGuide.com