title: Mechanical and pharmacological approaches to investigate the pathogenesis of Marfan syndrome in the abdominal aorta.
abstract: BACKGROUND
  Occurrence of disease complications in the abdominal aorta in Marfan syndrome, a connective tissue disorder caused by mutations in the gene encoding fibrillin-1, is relatively rare. We hypothesized that Marfan syndrome could affect the structure, vasomotor function and mechanical property of the abdominal aorta.
  
  
  RESULTS
  Abdominal aorta from mice at 3, 6, 9 and 12 months of age, heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1(C1039G/+), Marfan mice, n = 50), were compared with those from age-matched control littermates (n = 50). Marfan abdominal aorta demonstrated pronounced elastic fiber degradation and disorganization, concomitant with an increased aortic stiffness during aging. In the isometric force measurement, vasoconstriction in response to membrane depolarization or phenylephrine stimulation was similar in both Marfan and control abdominal aorta. However, Marfan abdominal aorta was less sensitive to the inhibition of the phenylephrine-induced contraction by indomethacin and SQ-29548, during which the release of thromboxane A(2) was one half of that of the controls. Nevertheless, the protein expression of cyclooxygenase-1 and cyclooxygenase-2 detected by Western immunoblotting was not different between the 2 strains.
  
  
  CONCLUSIONS
  We demonstrated that Marfan syndrome affected abdominal aorta with respect to matrix elastic fiber organization, aortic stiffness and release of thromboxane A(2).
authors.affiliation: Department of Cardiovascular Science, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. achung@mrl.ubc.ca
authors.forename: Ada W Y
authors.initials: AW
authors.lastname: Chung
authors.forename: H H Clarice
authors.initials: HH
authors.lastname: Yang
authors.forename: Karen Au
authors.initials: KA
authors.lastname: Yeung
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D066298:In Vitro Techniques; D008382:Marfan Syndrome / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D013928:Thromboxane A2 / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2