PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation

Angiogenesis
Roberto Gianni-BarreraAndrea Banfi

Abstract

VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting. Here we investigated the cellular mechanism by which PDGF-BB co-expression normalizes VEGF-induced aberrant angiogenesis. Monoclonal populations of transduced myoblasts, expressing similarly high levels of VEGF alone or with PDGF-BB, were implanted in mouse skeletal muscles. PDGF-BB co-expression did not promote sprouting and angiogenesis that occurred through vascular enlargement and splitting. However, enlargements were significantly smaller in diameter, due to a significant reduction in endothelial proliferation, and retained pericytes, which were otherwise lost with high VEGF alone. A time-course of histological analyses and repetitive intravital imaging showed that PDGF-BB co-expression antici...Continue Reading

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Citations

Jan 11, 2020·Stem Cells Translational Medicine·Roberto Gianni-BarreraAndrea Banfi
Mar 13, 2020·International Journal of Cancer. Journal International Du Cancer·Sarun JuengpanichXiujun Cai
May 23, 2020·International Journal of Cancer. Journal International Du Cancer·Qi HeMichael Welsh
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Apr 29, 2021·Cardiovascular Research·Willeke de HaanAernout Luttun
May 18, 2021·Frontiers in Physiology·Chun YaoBin Yu
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Jul 3, 2021·International Journal of Molecular Sciences·Jean-Luc Wautier, Marie-Paule Wautier
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Methods Mentioned

BETA
confocal microscopy
fluorescence microscopy
ELISA
Fluorescence
PCR
RNA assay
Protein Assay

Software Mentioned

LSM
CapImage
cellSens
GraphPad Prism
Imaris
GraphPad

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