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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:2083.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

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

From the Department of Pharmacology and Systems Therapeutics and the Cardiovascular Institute (L.C., F.R.), Mount Sinai School of Medicine, New York; the Department of Biomedical Engineering (J.E.W.), Saint Louis University, Mo; the Department of Cell Biology and Physiology (R.H.K., R.P.M.), Washington University School of Medicine, St. Louis, Mo; Université Joseph Fourier (B.M., G.F.), Grenoble, France; the Department of Anatomy and Cell Biology (E.C.D.), McGill University, Montreal, Canada; and the University of Texas Health Science Center (B.S.), Tyler.

Correspondence to Francesco Ramirez, PhD, Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, 1 Gustave L Levy Place, Box 1603, New York, NY 10029. E-mail francesco.ramirez{at}mssm.edu

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.

Mice with discrete deficiencies in elastic fiber components demonstrate the unique role of elastin in baseline blood pressure and vessel morphology, the discrete mechanical functions and overlapping material properties of fibrillin-1 and elastin in arterial tissues, and the involvement of fibrillin-1 in the hypertension-promoted remodeling of the elastin-deficient aorta.

Key Words: elastin • fibrillin-1 • hypertension • Marfan syndrome • supravalvular • aortic • stenosis