title: Altered in vitro endothelial repair and monocyte migration in obstructive sleep apnea: implication of VEGF and CRP.
abstract: OBJECTIVE
  Although obstructive sleep apnea (OSA) causes cardiovascular morbidities through atherosclerosis induced by inflammation and endothelial dysfunction, OSA patients exhibit elevated plasma vascular endothelial growth factor (VEGF), which may represent an adaptive response to intermittent hypoxia. The aims of this study were to investigate whether in vitro endothelial wound healing and monocyte migration are affected by patient serum, and to determine the implication of circulating factors (VEGF and C-reactive protein).
  
  
  METHODS
  Serum was collected from healthy controls (HC), "healthy" OSA, and metabolic syndrome (MS) patients with or without OSA.
  
  
  RESULTS
  Along with the presence of OSA and/or MS, both VEGF and hsCRP were significantly elevated in patient serum. Their specific role was tested with blocking antibodies on primary endothelial cells for wound healing assay and on human monocytes for migration assay. Endothelial wound healing was reduced with OSA compared to HC serum, and even more significantly using MS+OSA patient serum. Altered wound healing with OSA serum was unmasked when blocking VEGF and restored when blocking CRP. Monocyte migration was activated with OSA serum, and further enhanced by MS+OSA patient serum. Blocking CRP in serum inhibited this migration.
  
  
  CONCLUSIONS
  Serum from OSA patient alters in vitro endothelial cell repair function and activates monocyte migration; this is further aggravated with the presence of metabolic syndrome. These effects are partly driven by VEGF and CRP, suggesting an unfavorable balance between the pro healing (VEGF) and pro injury (CRP) factors that may promote vascular injury in OSA with and without metabolic syndrome.
authors.affiliation: Univ Grenoble Alpes, HP2, F-38000 Grenoble, France ; INSERM U1042, HP2, F-38000 Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Briançon-Marjollet
authors.affiliation: Univ Grenoble Alpes, HP2, F-38000 Grenoble, France ; INSERM U1042, HP2, F-38000 Grenoble, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Henri
authors.affiliation: Univ Grenoble Alpes, HP2, F-38000 Grenoble, France ; INSERM U1042, HP2, F-38000 Grenoble, France ; CHU de Grenoble, HP2, F-38000 Grenoble, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pépin
authors.affiliation: Univ Grenoble Alpes, HP2, F-38000 Grenoble, France ; INSERM U1042, HP2, F-38000 Grenoble, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Lemarié
authors.affiliation: Univ Grenoble Alpes, HP2, F-38000 Grenoble, France ; INSERM U1042, HP2, F-38000 Grenoble, France ; CHU de Grenoble, HP2, F-38000 Grenoble, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lévy
authors.affiliation: Univ Grenoble Alpes, HP2, F-38000 Grenoble, France ; INSERM U1042, HP2, F-38000 Grenoble, France ; CHU de Grenoble, HP2, F-38000 Grenoble, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Tamisier
mesh_terms: D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D000860:Hypoxia; D066298:In Vitro Techniques; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000473:pathology*; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D042461:Vascular Endothelial Growth Factor A; D002097:C-Reactive Protein
keywords: VEGF; endothelial repair; hsCRP; metabolic syndrome; obstructive sleep apnea