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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