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(Circulation Research. 2007;101:439.)
© 2007 American Heart Association, Inc.

Editorials

Bouncing Back From Elastin Deficiency

Pamela J. Ahmad, Lucy R. Osborne, Michelle P. Bendeck

From the Department of Laboratory Medicine and Pathobiology (P.J.A., M.P.B.), Institute of Medical Science (P.J.A., L.R.O., M.P.B.), and Department of Molecular and Medical Genetics (L.R.O.), University of Toronto, Ontario, Canada.

Correspondence to Michelle P. Bendeck, Professor, Career Investigator, Heart and Stroke Foundation of Ontario, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, Room 6213, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8. E-mail michelle.bendeck@utoronto.ca

See related article, pages 523–531

Key Words: aorta • cardiovascular disease • transgenic mice • vascular smooth muscle • elastin • supravalvular aortic stenosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Large arteries are comprised of vascular smooth muscle cells (SMCs) embedded within a complex, cell-derived extracellular matrix. Collagen and elastic fibers, the major constituents of the vascular matrix, are secreted and assembled by SMCs and confer tensile and elastic properties. In the medial layer of elastic arteries, elastin forms concentric fenestrated lamellar layers that intercalate with alternating rings of SMCs to form functional lamellar units.¹ In the aorta, elastic fibers represent the largest component of the extracellular matrix, contributing up to 50% of aortic dry weight.²

A series of elegant reports has demonstrated a critical role for elastin in the regulation of vascular morphogenesis in mice. Elastin (eln)-null mice die shortly after birth because of aortic obstruction by SMC proliferation.³ Heterozygous mice (eln^+/–) are viable but produce 50% less elastin mRNA and protein these animals are hypertensive, exhibit thinner elastic lamellae, more lamellar units, decreased aortic compliance, and mild cardiac hypertrophy compared with eln^+/+ mice.⁴ Extensive experimental studies have revealed that elevated arterial pressure is an adaptation to maintain cardiac output and tissue perfusion in spite of vessel stiffness,⁵ whereas the increase in lamellar unit number is an adaptation to normalize wall stress.⁶

In this issue of Circulation Research, Hirano et al report the phenotypic rescue of elastin-deficient mice by generation of a humanized elastin mouse.⁷ Using a bacterial artificial chromosome encoding the entire human elastin gene (hBAC), they engineered mice to express functional human elastin (ELN) under the control of its native . . . [Full Text of this Article]

Related Article:

Functional Rescue of Elastin Insufficiency in Mice by the Human Elastin Gene: Implications for Mouse Models of Human Disease

Eiichi Hirano, Russell H. Knutsen, Hideki Sugitani, Christopher H. Ciliberto, and Robert P. Mecham
Circ. Res. 2007 101: 523-531. [Abstract] [Full Text] [PDF]