title: Nonstenotic bicuspid aortic valve is associated with elevated plasma asymmetric dimethylarginine.
abstract: BACKGROUND
  Recently, it has been reported that nonstenotic bicuspid aortic valve (BAV) with dilated proximal aorta is linked with increased matrix metalloproteinase-2 (MMP-2) and endothelial dysfunction.
  
  
  OBJECTIVE
  We wondered whether asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, might be altered and associated with MMP-2 in BAV patients. We assessed the relation between ADMA levels and aortic diameters and hypothesized that elevated ADMA might be an independent predictor of progressive aortic dilatation in BAV patients.
  
  
  METHODS
  We studied 20 patients with nonstenotic BAV (17 men and 3 women, median age 27, range 24-33 years). Twenty age-matched patients with tricuspid aortic valves served as controls. Plasma levels of ADMA, symmetric dimethylarginine (SDMA), L-arginine, serum MMP-2, MMP-9, and plasma total homocysteine (tHcy), together with parameters of aortic elasticity, were measured.
  
  
  RESULTS
  ADMA and MMP-2 levels were higher in the BAV group compared with controls (medians, 0.55 vs. 0.43 μmol/l, P < 0.001 and 1.25 vs. 1.00 μmol/l, P < 0.001, respectively). The BAV patients also had higher SDMA and tHcy levels than controls (0.39 vs. 0.35 μmol/l, P < 0.001 and 11.5 vs. 9.7 μmol/l, P = 0.006). ADMA levels in BAV patients correlated with aortic annulus (r = 0.4, P = 0.043), peak aortic velocity (r = 0.6, P = 0.001), aortic distensibility (r = 0.6, P = 0.004), aortic stiffness index (r = 0.7, P < 0.001), and aortic strain (r = 0.7, P < 0.001) as well as with MMP-2 (r = 0.6, P = 0.002) and tHcy (r = 0.4, P = 0.042).
  
  
  CONCLUSIONS
  This study is the first to show that circulating ADMA together with MMP-2 is a marker of proximal ascending aortic dilatation and impaired aortic elastic properties in nonstenotic BAV patients. It might be speculated that plasma ADMA could be helpful in identifying BAV patients at a higher risk of aortic aneurysm.
authors.affiliation: The John Paul II Hospital, Krakow, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Drapisz
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Góralczyk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jamka-Miszalski
authors.forename: Maria
authors.initials: M
authors.lastname: Olszowska
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D000328:Adult; D001011:Aorta / Q000473:pathology; D001014:Aortic Aneurysm / Q000097:blood / Q000209:etiology / Q000473:pathology; D001021:Aortic Valve / Q000002:abnormalities / Q000473:pathology; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004108:Dilatation, Pathologic; D005260:Female; D006349:Heart Valve Diseases / Q000097:blood* / Q000150:complications / Q000473:pathology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D015854:Up-Regulation; D059289:Vascular Stiffness; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9