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Propranolol targets the contractility of infantile haemangioma-derived pericytes

D Lee1, E Boscolo, J T Durham

  • 1Vascular Biology Program and Department of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, U.S.A.

The British Journal of Dermatology
|April 12, 2014
PubMed

Insights

Propranolol treatment for infantile haemangioma (IH) may work by increasing pericyte contractility. This study investigated haemangioma pericytes and found propranolol enhances their contractile response, suggesting a key mechanism in IH regression.

Area of Science:

  • Vascular Biology
  • Pharmacology
  • Developmental Biology

Background:

  • Propranolol is a β-adrenergic receptor (AR) antagonist used to treat infantile haemangioma (IH).
  • Rapid fading of IH color and accelerated vessel regression occur after propranolol initiation.

Purpose of the Study:

  • To investigate the role of haemangioma-derived pericytes (HemPericytes) in propranolol-induced vasoconstriction.
  • To assess HemPericytes from proliferating and involuting IH tumors.

Main Methods:

  • Assayed HemPericyte contractility on a silicone substrate.
  • Used small interfering RNA to knock down β2-AR and observed effects of propranolol and epinephrine.
  • Co-implanted HemPericytes and endothelial cells in mice, then treated with propranolol or vehicle.

Main Results:

  • HemPericytes showed high β2-AR mRNA levels, higher than other AR subtypes.
  • Propranolol (10 μmol L(-1)) restored contractility in relaxed HemPericytes.
  • Propranolol inhibited HemPericyte proliferation in vitro.
  • Contrast-enhanced microultrasonography revealed decreased vascular volume in propranolol-treated mice.

Conclusions:

  • Findings suggest propranolol's mechanism in proliferating IH involves enhanced pericytic contractility.
  • This effect appears specific to haemangioma pericytes, as normal pericytes were unaffected in contractility assays.
Abstract

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