Propranolol targets the contractility of infantile haemangioma-derived pericytes.

D Lee, E Boscolo, J T Durham, J B Mulliken, I M Herman, J Bischoff

Index: Br. J. Dermatol. 171(5) , 1129-37, (2014)

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Abstract

Propranolol, a β-adrenergic receptor (AR) antagonist, is an effective treatment for endangering infantile haemangioma (IH). Dramatic fading of cutaneous colour is often seen a short time after initiating propranolol therapy, with accelerated regression of IH blood vessels discerned after weeks to months.To assess a possible role for haemangioma-derived pericytes (HemPericytes) isolated from proliferating and involuting phase tumours in apparent propranolol-induced vasoconstriction.HemPericytes were assayed for contractility on a deformable silicone substrate: propranolol (10 μmol L(-1)) restored basal contractile levels in HemPericytes that were relaxed with the AR agonist epinephrine. Small interfering RNA knockdown of β2-AR blunted this response. HemPericytes and haemangioma-derived endothelial cells were co-implanted subcutaneously in nude mice to form blood vessels; at day 7 after injection, mice were randomized into vehicle and propranolol-treated groups.HemPericytes expressed high levels of β2-AR mRNA compared with positive control bladder smooth muscle cells. In addition, β2-AR mRNA levels were relatively high in IH specimens (n = 15) compared with β1-AR, β3-AR and α1b-AR. Normal human retinal and placental pericytes were not affected by epinephrine or propranolol in this assay. Propranolol (10 μmol L(-1)) inhibited the proliferation of HemPericytes in vitro, as well as normal pericytes, indicating a nonselective effect in this assay. Contrast-enhanced microultrasonography of the implants after 7 days of treatment showed significantly decreased vascular volume in propranolol-treated animals, but no reduction in vehicle-treated animals.These findings suggest that the mechanism of propranolol's effect on proliferating IH involves increased pericytic contractility.© 2014 British Association of Dermatologists.