Research Paper

Mechanical and Pharmacological Approaches to Investigate the Pathogenesis of Marfan Syndrome in the Abdominal Aorta
Ada W.Y. Chung, H.H. Clarice Yang, Karen Au Yeung, Cornelis van Breemen

Department of Cardiovascular Science, Child and Family Research Institute and Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, B.C., Canada

Address of Corresponding Author

J Vasc Res 2008;45:314-322 (DOI: 10.1159/000113603)

  Key Words

• Marfan syndrome
• Abdominal aorta
• Cyclooxygenase
• Elastic fiber
• Aortic stiffness
• Vasomotor function

  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. Methods and 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 A₂ 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 A₂.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Dr. Ada W.Y. Chung
Department of Cardiovascular Science, University of British Columbia
Room 2099, 950 28th W Ave
Vancouver, BC V5Z 4H4 (Canada)
Tel. +1 604 875 3852, Fax +1 604 875 3120, E-Mail achung@mrl.ubc.ca

  Article Information

Received: July 12, 2007
Accepted after revision: October 19, 2007
Published online: January 22, 2008
Number of Print Pages : 9
Number of Figures : 7, Number of Tables : 2, Number of References : 41