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Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2083-9. doi: 10.1161/ATVBAHA.109.193227. Epub 2009 Oct 22.

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

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1
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.

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 supravalvular 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.

PMID:
19850904
PMCID:
PMC2797476
DOI:
10.1161/ATVBAHA.109.193227
[Indexed for MEDLINE]
Free PMC Article
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