title: Associations of vascular endothelial growth factor (VEGF) with adhesion and inflammation molecules in a healthy population.
abstract: Vascular endothelial growth factor (VEGF) is implicated in numerous pathologies through complex relationships with cellular adhesion molecules (CAMs) and inflammation markers. These have not been assessed in non-pathological conditions. Our aim was the evaluation of associations between VEGF and CAM/inflammation molecules in a healthy population, and of possible genomic interplays in order to better apprehend the underlying mechanisms leading to the pathology. We examined the associations between VEGF and ICAM-1, VCAM-1, E-, L-, P-selectins, TNF-α, CRP and IL-6 plasma levels in 403 healthy individuals. Gene expression of CAM/inflammation molecules and VEGF isoforms (121, 145, 165, and 189) were quantified in peripheral blood mononuclear cells (PBMCs). The effect of four genetic variants (explaining ≈ 50% of the heritability of circulating VEGF levels) and of their interactions on plasma and mRNA levels of CAM/inflammation molecules was examined. VEGF was associated with ICAM-1 and E-selectin in plasma. In PBMCs, VEGF(145) mRNA was associated with ICAM-1, L-selectin and TNF-α expression. Interactions of the genetic variants were shown to affect ICAM-1, E-selectin, IL-6 and TNF-α plasma levels, while rs4416670 was associated with L-selectin expression. These findings propose a biological connection between VEGF and CAM/inflammation markers. Common genetic and transcriptional mechanisms may link these molecules and control their effect in healthy conditions.
authors.affiliation: Cardiovascular Genetics Research Unit, EA4373, University of Lorraine, F-54000 Nancy, France.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Azimi-Nezhad
authors.forename: Maria G
authors.initials: MG
authors.lastname: Stathopoulou
authors.forename: Amélie
authors.initials: A
authors.lastname: Bonnefond
authors.forename: Marc
authors.initials: M
authors.lastname: Rancier
authors.forename: Abdelsalam
authors.initials: A
authors.lastname: Saleh
authors.forename: John
authors.initials: J
authors.lastname: Lamont
authors.forename: Peter
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: Ndeye Coumba
authors.initials: NC
authors.lastname: Ndiaye
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D019040:E-Selectin / Q000097:blood / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006262:Health; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D015850:Interleukin-6; D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A