Discrete contributions of elastic fiber components to arterial development and mechanical compliance

Luca Carta, Jessica E. Wagenseil, Russell H. Knutsen, Boubacar Mariko, Gilles Faury, Elaine C. Davis, Barry Starcher, Robert P. Mecham, Francesco Ramirez

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

OBJECTIVE-: Even though elastin and fibrillin-1 are the major structural components of elastic fibers, mutations in elastin and fibrillin-1 lead to narrowing of large arteries in supravascular aortic stenosis and dilation of the ascending aorta in Marfan syndrome, respectively. A genetic approach was therefore used here to distinguish the differential contributions of elastin and fibrillin-1 to arterial development and compliance. METHODS AND RESULTS-: Key parameters of cardiovascular function were compared among adult mice haploinsufficient for elastin (Eln), fibrillin-1 (Fbn1), or both proteins (dHet). Physiological and morphological comparisons correlate elastin haploinsufficiency with increased blood pressure and vessel length and tortuosity in dHet mice, and fibrillin-1 haploinsufficiency with increased aortic diameter in the same mutant animals. Mechanical tests confirm that elastin and fibrillin-1 impart elastic recoil and tensile strength to the aortic wall, respectively. Additional ex vivo analyses demonstrate additive and overlapping contributions of elastin and fibrillin-1 to the material properties of vascular tissues. Lastly, light and electron microscopy evidence implicates fibrillin-1 in the hypertension-promoted remodeling of the elastin-deficient aorta. CONCLUSIONS-: These results demonstrate that elastin and fibrillin-1 have both differential and complementary roles in arterial wall formation and function, and advance our knowledge of the structural determinants of vascular physiology and disease.

Original languageEnglish
Pages (from-to)2083-2089
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Aortic
  • Elastin
  • Fibrillin-1
  • Hypertension
  • Marfan syndrome
  • Stenosis
  • Supravalvular

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