title: Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF.
  
  
  OBJECTIVE
  The objective of this study was to explore if circulating relaxin-2 in male OSA subjects may be related to OSA severity, to circulating levels of MMPs, of their inhibitors (tissue inhibitors of metalloproteinases; TIMPs), and of VEGF, and if it may protect from hypertension.
  
  
  METHODS
  Fifty untreated male subjects with suspected OSA were recruited. After nocturnal polysomnography, a morning venous blood sample was withdrawn. Then, 24-hour ambulatory blood pressure (BP) monitoring was performed.
  
  
  RESULTS
  The respiratory disturbance index in the sample was 30.4 [interquartile range (IQR) 15.6-55.2]. Relaxin-2 was detectable in 20 subjects. These subjects did not differ in OSA severity or diurnal and nocturnal BP from subjects with undetectable relaxin-2, but they showed lower TIMP-1 (126.8 ± 29.1 vs. 156.9 ± 41.7 pg/ml, respectively; p = 0.007) and a marginally higher MMP-9/TIMP-1 molar ratio [0.58 (IQR 0.23-1.35) vs. 0.25 (IQR 0.15-0.56); p = 0.052].
  
  
  CONCLUSIONS
  Relaxin-2 in male subjects was not related to OSA severity, but it was associated with lower TIMP-1. As it was often undetectable, even when BP values were normal, it is unlikely that it plays a role as a major factor protecting from hypertension in OSA.
authors.affiliation: National Research Council, Institute of Biomedicine and Molecular Immunology x2018;A. Monroy', Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bonanno
authors.forename: Loredana
authors.initials: L
authors.lastname: Riccobono
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Bonsignore
authors.forename: Anna
authors.initials: A
authors.lastname: Lo Bue
authors.forename: Adriana
authors.initials: A
authors.lastname: Salvaggio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Insalaco
authors.forename: Oreste
authors.initials: O
authors.lastname: Marrone
mesh_terms: D000328:Adult; D001794:Blood Pressure; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications; D000860:Hypoxia / Q000097:blood* / Q000209:etiology; D007249:Inflammation; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D017286:Polysomnography; D012065:Relaxin / Q000097:blood*; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000150:complications; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D018836:Inflammation Mediators; C095068:RLN2 protein, human; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D012065:Relaxin; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9