title: Increased plasma YKL-40/chitinase-3-like-protein-1 is associated with endothelial dysfunction in obstructive sleep apnea.
abstract: OBJECTIVE
  Obstructive sleep apnea (OSA) is a common disorder affecting 15-24% of the adults and is associated with increased risk of hypertension and atherosclerosis. The exact mechanisms underlying hypertension in OSA are not entirely clear. YKL-40/Chitinase-3-like protein-1 is a circulating moiety with roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis and a number of other diseases. We sought to determine the role of YKL-40 in endothelial dysfunction and hypertension in OSA.
  
  
  METHODS
  We studies 23 normotensive OSA (N-OSA) and 14 hypertensive OSA (H-OSA) without diabetes and apparent cardiovascular disease. Endothelial-dependent nitric oxide-mediated vasodilatory capacity was assessed by flow-mediated vasodilation (FMD). YKL-40, vascular endothelial growth factor (VEGF) and the soluble form of VEGF receptor-1 or sFlt-1 were measured in plasma using ELISA methodology.
  
  
  RESULTS
  N-OSA subjects aged 49.1 ± 2.3 years and H-OSA aged 51.3 ± 1.9 years with BMI 36.1 ± 1.6 and 37.6 ± 1.9 kg/m(2), respectively. The apnea-hypopnea index (AHI) was 41 ± 5 events/hr in N-OSA and 46 ± 6 in H-OSA with comparable degree of oxygen desaturations during sleep. FMD was markedly impaired in H-OSA (8.3% ± 0.8) compared to N-OSA (13.2% ± 0.6, P<0.0001). Plasma YKL-40 was significantly elevated in H-OSA (55.2 ± 7.9 ng/ml vs. 35.6 ± 4.2 ng/ml in N-OSA, P = 0.02) and had an inverse relationship with FMD (r = -0.52, P = 0.013). There was a significant positive correlation between sFlt-1/VEGF, a measure of decreased VEGF availability, and YKL-40 (r = 0.42, P = 0.04).
  
  
  CONCLUSIONS
  The levels of plasma YKL-40 were elevated in H-OSA group and inversely correlated with the endothelial-dependent vasodilatory capacity whereas there was a positive correlation between sFlt-1/VEGF and YKL-40. These findings suggest that YKL-40 is dysregulated, in part, due to perturbation of VEGF signaling, and may contribute to endothelial dysfunction and hypertension in OSA.
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, University of California, Irvine, California, United States of America.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Jafari
authors.affiliation: Warren Alpert School of Medicine, Providence, Rhode Island, United States of America.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine and 4 John B. Pierce Laboratory, New Haven, Connecticut, United States of America.
authors.forename: Vahid
authors.initials: V
authors.lastname: Mohsenin
mesh_terms: D054392:Adipokines / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism / Q000473:pathology; D000071451:Chitinase-3-Like Protein 1; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism / Q000473:pathology; D037102:Lectins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen