title: Endothelial function, carotid-femoral stiffness, and plasma matrix metalloproteinase-2 in men with bicuspid aortic valve and dilated aorta.
abstract: OBJECTIVE
  This study sought to examine the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV).
  
  
  BACKGROUND
  Proximal aortic dilation in subjects with BAV is associated with structural and functional abnormalities in the ascending aorta.
  
  
  METHODS
  We studied 32 men (median age 31 years [range 28 to 32 years]) with nonstenotic BAV categorized into 2 subgroups according to proximal ascending aorta dimensions (nondilated <or=35 mm and dilated >or=40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia (a marker of endothelial dysfunction) and carotid-femoral pulse wave velocity (an index of aortic stiffness) were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively.
  
  
  RESULTS
  Despite the similar severity of aortic stenosis, left ventricular mass, and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4% to 6%] vs. 8% [IQR 7% to 9%] change, p = 0.001), higher carotid-femoral pulse wave velocity (9.3 cm/s [IQR 9 to 10 cm/s] vs. 7 cm/s [IQR 6.9 to 7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460 to 1,674] vs. 1,036 [IQR 962 to 1,167], p = 0.001) compared with men with BAV and nondilated aorta. Values for MMP-9, TIMP-1 and -2 levels, and nitroglycerin-induced (endothelium-independent) vasodilation were similar in all 3 groups.
  
  
  CONCLUSIONS
  Young men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid-femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention.
authors.affiliation: Division of Cardiology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tzemos
authors.forename: Erik
authors.initials: E
authors.lastname: Lyseggen
authors.forename: Candice
authors.initials: C
authors.lastname: Silversides
authors.forename: Michal
authors.initials: M
authors.lastname: Jamorski
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Tong
authors.forename: Paula
authors.initials: P
authors.lastname: Harvey
authors.forename: John
authors.initials: J
authors.lastname: Floras
authors.forename: Samuel
authors.initials: S
authors.lastname: Siu
mesh_terms: D000328:Adult; D001011:Aorta / Q000473:pathology* / Q000503:physiopathology; D001021:Aortic Valve / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004108:Dilatation, Pathologic; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005263:Femoral Artery / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D005996:Nitroglycerin; D011673:Pulsatile Flow / Q000502:physiology*; D013599:Systole / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D014463:Ultrasonography; D014665:Vasodilator Agents
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D014665:Vasodilator Agents; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005996:Nitroglycerin