Pericytes from infantile hemangioma display proangiogenic properties and dysregulated angiopoietin-1

Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):501-9. doi: 10.1161/ATVBAHA.112.300929. Epub 2013 Jan 3.

Abstract

Objective: Infantile hemangioma (IH) is a rapidly growing vascular tumor affecting newborns. It is composed of immature endothelial cells and pericytes that proliferate into a disorganized mass of blood vessels. We isolated pericytes from IH (Hem-pericytes) to test our hypothesis that Hem-pericytes are unable to stabilize blood vessels.

Methods and results: We injected pericytes in vivo, in combination with endothelial cells, and found that Hem-pericytes formed more microvessels compared with control retinal pericytes. We, thereby, analyzed proangiogenic properties of the Hem-pericytes. They grew fast in vitro, and were unable to stabilize endothelial cell growth and migration, and expressed high levels of vascular endothelial growth factor-A compared with retinal pericytes. Hem-pericytes from proliferating phase IH showed lower contractility in vitro, compared with Hem-pericytes from the involuting phase and retinal pericytes. Consistent with a diminished ability to stabilize endothelium, angiopoietin 1 was reduced in Hem-pericytes compared with retinal pericytes. Normal retinal pericytes in which angiopoietin 1 was silenced produced conditioned medium that stimulated endothelial cell proliferation and migration.

Conclusions: We report the first successful isolation of patient-derived pericytes from IH tissue. Hem-pericytes exhibited proangiogenic properties and low levels of angiopoietin 1, consistent with a diminished ability to stabilize blood vessels in IH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Cell Communication
  • Cell Movement
  • Cell Proliferation
  • Cell Separation / methods
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Down-Regulation
  • Hemangioma / metabolism*
  • Hemangioma / pathology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / transplantation
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic*
  • Pericytes / metabolism*
  • Pericytes / pathology
  • Pericytes / transplantation
  • RNA Interference
  • RNA, Messenger / metabolism
  • Retinal Vessels / metabolism
  • Time Factors
  • Transfection
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • Biomarkers
  • Culture Media, Conditioned
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A