title: Interactions between inflammatory activation and endothelial dysfunction selectively modulate valve disease progression in patients with bicuspid aortic valve.
abstract: OBJECTIVE
  Bicuspid aortic valve (BAV) is associated with increased risk of valvular degeneration and ascending aortic aneurysm formation and rupture. We sought to evaluate the roles of endothelial dysfunction and inflammatory activation in modulating these processes.
  
  
  METHODS
  We performed a case-control study of patients with BAV together with a multivariate analysis within the BAV group to identify factors associated with: development of significant valvular disease; dilatation of the ascending aorta; differential valve relative to aortic disease. Endothelial function of patients and controls was evaluated via flow-mediated dilatation (FMD) and plasma concentrations of asymmetric dimethylarginine (ADMA). Correlations with inflammatory markers and endothelial progenitor cell counts were also examined. Morphological and physiological assessment of the valve and ascending aorta was performed with transthoracic echocardiography and MRI.
  
  
  RESULTS
  Patients with BAV (n=43) and controls (n=25) were matched for age and gender. FMD was significantly lower in patients than controls (7.85±3.48% vs 11.58±3.98%, p=0.001), and these differences were age-independent. Within the BAV cohort, multivariate correlates of peak aortic valve velocity were plasma concentrations of ADMA and myeloperoxidase (MPO) (both p<0.01), while increasing age was an independent correlate of ascending aortic diameter (p<0.05). Furthermore, both low FMD and inflammatory activation were multivariate correlates of selectivity for valvular disease.
  
  
  CONCLUSIONS
  BAV is associated with endothelial dysfunction. The extent of inflammatory activation (specifically MPO release) and that of endothelial dysfunction impact primarily on integrity of the valve rather than aortic structure.
authors.affiliation: Department of Cardiology, The Queen Elizabeth Hospital, , Adelaide, Australia.
authors.forename: Onn Akbar
authors.initials: OA
authors.lastname: Ali
authors.forename: Matthew
authors.initials: M
authors.lastname: Chapman
authors.forename: Thanh Ha
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Yuliy Y
authors.initials: YY
authors.lastname: Chirkov
authors.forename: Tamila
authors.initials: T
authors.lastname: Heresztyn
authors.forename: Juan
authors.initials: J
authors.lastname: Mundisugih
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D001011:Aorta / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001021:Aortic Valve / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000378:metabolism*; D018450:Disease Progression; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006349:Heart Valve Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009195:Peroxidase / Q000097:blood; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014664:Vasodilation / Q000502:physiology*
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine; D009195:Peroxidase; D019001:Nitric Oxide Synthase