on October 22, 2009
Published online before print October 22, 2009, doi: 10.1161/ATVBAHA.109.193227
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Submitted on June 16, 2009
Accepted on October 11, 2009
Discrete Contributions of Elastic Fiber Components to Arterial Development and Mechanical Compliance
Luca Carta ;
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.
* To whom correspondence should be addressed. 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.
Key words: elastin • fibrillin-1 • hypertension • Marfan syndrome • supravalvular • aortic • stenosis