title: CSF profiles of angiogenic and inflammatory factors depend on the respiratory status of ALS patients.
abstract: Our objective was to assess the regulation of the hypoxia response of angiogenic and inflammatory factors from 76 cerebrospinal fluids (CSF) of sporadic amyotrophic lateral sclerosis (ALS) patients with different respiratory status. We first analysed the hypoxia response capacity by measuring CSF levels of angiogenin (ANG), VEGF, angiopoietin-2 (ANG-2) and PGE-2 in 40 ALS patients according to their hypoxaemia level and compared it with 40 neurological controls. We then compared the ANG, VEGF, EPO and ANG-2 CSF levels of 36 other ALS patients, divided into three groups with either 1) normoxaemia, 2) intermittent desaturation in the absence of hypoxaemia, or 3) chronic hypoxaemia with or without desaturation. We demonstrated a lack of up-regulation of both ANG and VEGF during hypoxaemia in ALS, compared with hypoxaemic controls. In contrast, PGE-2 and ANG-2 levels were increased in both hypoxaemic ALS patients and controls. ANG and VEGF levels did not increase in patients with long disease durations and with intermittent or chronic hypoxaemia. ANG-2 and EPO levels were up-regulated early in intermittent hypoxaemia and late in chronic hypoxaemia, respectively. Our results suggest alteration of the HIF-1alpha-mediated response to hypoxia during sporadic ALS, whereas the NFK-B pathway seems early activated.
authors.affiliation: Service de Neurologie et Pathologie du Mouvement, Hôpital Roger Salengro, CHRU, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moreau
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Véronique
authors.initials: V
authors.lastname: Brunaud-Danel
authors.forename: Philippe
authors.initials: P
authors.lastname: Lassalle
authors.forename: Benoist
authors.initials: B
authors.lastname: Degonne
authors.forename: Alain
authors.initials: A
authors.lastname: Destee
authors.forename: Luc
authors.initials: L
authors.lastname: Defebvre
authors.forename: David
authors.initials: D
authors.lastname: Devos
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid*; D042702:Angiopoietin-2 / Q000134:cerebrospinal fluid; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D004921:Erythropoietin / Q000134:cerebrospinal fluid; D006801:Humans; D000860:Hypoxia; D007249:Inflammation / Q000134:cerebrospinal fluid; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D012119:Respiration; D012259:Ribonuclease, Pancreatic / Q000134:cerebrospinal fluid; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid
chemical_list: D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D015232:Dinoprostone; D010100:Oxygen