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VEGF‐A Induces a CD36 low Endothelial Cell Phenotype by Activating a MAPK‐Dependent Pathway: Novel Mechanism for Sustaining Proliferation in the Presence of TSP‐1
Author(s) -
Anderson Christopher Richard,
Hastings Nikki,
Blackman Brett R.,
Price Richard J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.49.5
Subject(s) - cd36 , umbilical vein , downregulation and upregulation , mapk/erk pathway , angiogenesis , microbiology and biotechnology , thrombospondin 1 , signal transduction , chemistry , human umbilical vein endothelial cell , phenotype , vascular endothelial growth factor a , receptor , biology , cancer research , vascular endothelial growth factor , biochemistry , vegf receptors , in vitro , gene
We have shown that, in a rat model of inflammation‐induced angiogenesis, capillary sprout endothelial cells (EC) markedly downregulate CD36, a receptor for the anti‐angiogenic molecule thrombospondin‐1 (TSP‐1). The expression of VEGF‐A, a known regulator of angiogenic phenotype, increases in this model (2.5‐fold by ELISA), so we tested the hypothesis that VEGF‐A directly regulates the CD36‐phenotype. Human umbilical vein endothelial cells (HUVECS) exposed to VEGF‐A (50 ng/ml) exhibited a significant 60% decrease in CD36 mRNA and protein expression after 24 h. This effect was dependent on VEGFR‐2 and MAPK, as pharmacological inhibitors of these signaling molecules (SU5416, UO126, PD98058) restored CD36 expression in VEGF‐A treated cells. Importantly, HUVECS that had been pre‐conditioned to a CD36low phenotype became insensitive to inhibitory TSP‐1 signaling due to the loss of CD36 expression. These results identify the downregulation of CD36 via the activation of a MAPK‐dependent signaling pathway as a novel mechanism through which VEGF‐A can sustain EC proliferation in the presence of TSP‐1. Supported by NIH HL74082 and NIH HL65958.