Premium
OxLDL Exerts A Biphasic Effect on Endothelial Function: A Role for Oxidised Lipids in Angiogenesis and Inflammation
Author(s) -
Olding Michael,
ArdernJones Michael R,
Healy Eugene,
Millar Timothy M
Publication year - 2016
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.30.1_supplement.165.9
Subject(s) - angiogenesis , s1pr1 , inflammation , cd36 , scavenger receptor , endothelial stem cell , chemistry , receptor , lipoprotein , endothelium , sphingosine 1 phosphate , microbiology and biotechnology , endocrinology , medicine , sphingosine , biology , immunology , vascular endothelial growth factor a , cancer research , cholesterol , biochemistry , vascular endothelial growth factor , in vitro , vegf receptors
Oxidised lipids are known to promote inflammation and are implicated in the pathophysiology of psoriasis, promoting cardiovascular disease. The deleterious effects of oxidised low‐density lipoprotein (oxLDL) are potentially mediated through vascular cell activation. We therefore tested the hypothesis that serum lipids, LDL and its oxidation products can modify endothelial cell function. The effects of serum lipids and oxLDL on primary human endothelial cells were assessed in assays for migration, angiogenesis, leukocyte recruitment and vascular cell surface receptor expression. Our results showed that at relatively high concentrations oxLDL inhibited angiogenesis and endothelial migration. However, lower concentrations of oxLDL stimulated endothelial migration. In contrast, oxLDL caused increased leukocyte recruitment to the endothelium under shear stress only at higher concentration. Native LDL was shown to have no effect at equivalent concentrations in these assays. Serum lipids were also shown to regulate endothelial function as their removal from cultures inhibited endothelial migration and angiogenesis. However, removal of serum lipids did not impair the ability of cytokine‐stimulated endothelial cells to recruit flowing leukocytes. Analysis of known oxLDL receptor‐1 (LOX‐1) and scavenger receptor B (CD36) showed minimal expression in these cells. A potential mechanism through which oxLDL mediates its activity involves the stimulation of sphingosine metabolism. Initial studies have revealed sphingosine‐1‐phosphate receptor (S1PR1) expression in endothelial cells and is currently under investigation for oxLDL mediated effects. In conclusion, these data suggest an important role for circulating lipids and lipoproteins in the regulation of endothelial function, which may have implications for psoriatic pathology and cardiovascular disease. Support or Funding Information Funded by The Psoriasis Association, UK