Angiogenesis

, Volume 10, Issue 1, pp 35–45

An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis

  • Daniela Virgintino
  • Francesco Girolamo
  • Mariella Errede
  • Carmen Capobianco
  • David Robertson
  • William B. Stallcup
  • Roberto Perris
  • Luisa Roncali
Original Paper

Abstract

In order to better understand the process of angiogenesis in the developing human brain, we have examined the spatial relationship and relative contributions of endothelial cells and pericytes, the two primary cell types involved in vessel growth, together with their relation with the vascular basement membrane. Pericytes were immunolocalized through use of the specific markers nerve/glial antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth factor receptor β (PDGFR-β), while endothelial cells were identified by the pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis demonstrates that microvessels of the fetal human telencephalon are characterized by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest endothelial cells and participate in the earliest stages of vessel growth. Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti-collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and pericytes are both associated with the vascular basement membrane during vessel sprouting. Detailed localization of the two vascular cell types during angiogenesis suggests that growing microvessels of the human telencephalon are formed by a pericyte-driven angiogenic process in which the endothelial cells are preceded and guided by migrating pericytes during organization of the growing vessel wall.

Keywords

Angiogenesis Basement membrane Endosialin Endothelial cells Human brain MMP-2 NG2 PDGFR-β Pericytes 

Abbreviations

aMMP-2

Active matrix metalloproteinase-2

BB

Blocking buffer

BBB

Blood–brain barrier

CD31

PECAM-1

CNS

Central nervous system

ECM

Extracellular matrix

GLUT-1

Glucose transporter isoform 1

mAb

Monoclonal antibody

NG2

Nerve/glial antigen 2

pAb

Polyclonal antibody

PBS

Phosphate-buffered saline

PDGFR-β

Platelet-derived growth factor receptor β

VEGF

Vascular endothelial growth factor

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Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  • Daniela Virgintino
    • 1
  • Francesco Girolamo
    • 1
  • Mariella Errede
    • 1
  • Carmen Capobianco
    • 2
  • David Robertson
    • 3
  • William B. Stallcup
    • 4
  • Roberto Perris
    • 5
    • 6
  • Luisa Roncali
    • 1
  1. 1.Department of Human Anatomy and HistologyUniversity of Bari School of MedicineBariItaly
  2. 2.Department of Emergency and Organ TransplantationUniversity of Bari School of MedicineBariItaly
  3. 3.The Breakthrough Breast Cancer Research CentreInstitute of Cancer ResearchLondonUK
  4. 4.The Burnham Institute for Medical ResearchLa JollaUSA
  5. 5.Department of Evolutionary and Functional BiologyUniversity of ParmaParmaItaly
  6. 6.Division for Experimental Oncology 2The National Cancer Institute of Aviano, CRO-IRCCSAvianoItaly

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