Format

Send to

Choose Destination
See comment in PubMed Commons below
Cardiovasc Res. 2013 Dec 1;100(3):492-500. doi: 10.1093/cvr/cvt215. Epub 2013 Sep 16.

Pericytes modulate endothelial sprouting.

Author information

1
Department of Medicine and Section of Nephrology, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

AIM:

Angiogenic sprouts arise from microvessels formed by endothelial cells (ECs) invested by pericytes (PCs). The aim of this study was to examine the role of PCs in angiogenic sprouting, an understudied phenomenon.

METHODS AND RESULTS:

We adapted a human EC spheroid model to examine PC effects on vascular endothelial growth factor-A-induced EC sprouting in vitro by using Bcl-2-transduced human umbilical vein ECs to reduce apoptosis in collagen gels. Human placental PCs, separated from endothelial spheroids by a transwell, or addition of PC-conditioned media increased EC sprouting primarily through hepatocyte growth factor (HGF). Mixed endothelial-PC spheroids formed similar numbers of endothelial sprouts as endothelial spheroids but the sprouts from mixed spheroids were invested by PCs within 24 h. PCs were recruited to the sprouts by platelet-derived growth factor (PDGF)-BB; inhibition of PDGF signalling reduced PC coverage and increased EC sprouting. Transplanted endothelial spheroids give rise to sprouts in vivo that evolve into perfused microvessels. Mixed endothelial-PC spheroids form similar numbers of microvessels as endothelial-only spheroids, but acquire human PC investment and have reduced average lumen diameter.

CONCLUSIONS:

PCs promote endothelial sprouting by elaborating HGF, but when recruited to invest endothelial sprouts by PDGF-BB, limit the extent of sprouting in vitro and lumen diameter in vivo.

KEYWORDS:

Bcl-2; Endothelial cells; Hepatocyte growth factor; Pericytes; Platelet-derived growth factor

PMID:
24042014
PMCID:
PMC3826704
DOI:
10.1093/cvr/cvt215
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center