Brief reviews
New Insights into Elastin and Vascular Disease

https://doi.org/10.1016/S1050-1738(03)00065-3Get rights and content

Abstract

Elastin is synthesized and secreted by vascular smooth muscle cells and is the major extracellular matrix component deposited in the arterial wall. When last reviewed by this journal in 1994, the link between elastin and a rare occlusive vascular disease had just been established. Since that time, it has become increasingly clear that elastin is a critical autocrine factor that maintains vascular homeostasis through a combination of biomechanical support and biologic signaling. This review examines the complexity of elastin–smooth muscle cell interactions, and how new insights may impact understanding of the pathogenesis and treatment of vascular disease.

Section snippets

Elastin Haploinsufficiency Causes Vascular Disease

SVAS may occur either as an isolated condition or as part of the complex developmental disorder, WBS. When researchers Curran et al. 1993, Ewart et al. 1993, Ewart et al. 1994 initially described the human molecular genetics for SVAS and WBS, they reported balanced translocations and microdeletions within the elastin (ELN) gene locus. Over the past 10 years, however, it has become clear that other loss-of-function mutations in elastin also cause SVAS. To define the spectrum of ELN mutations

Elastin Regulates VSMC Activity in Vitro and in Vivo

It is well established that VSMCs in a mature artery exist in a quiescent contractile state, but can dedifferentiate to a noncontractile state under circumstances of injury, repair, or regeneration Raines and Ross 1993, Thyberg 1998. This immature smooth muscle phenotype is characterized by an increased rate of proliferation, migration, and secretion of fibrous ECM. The role of elastin in regulating VSMC proliferation, migration, and differentiation has been explored through numerous in vitro

Molecular Mechanism of Elastin–VSMC Signaling

The experiments detailed above strongly suggest a molecular signaling interaction between elastin and VSMCs. Identifying the membrane receptor and intracellular signaling pathway responsible for mediating elastin–VSMC interactions has been the subject of much research over the past 2 decades. Initially, a 67-kDa elastin binding protein (EBP) anchored to the plasma membrane by 61-kDa and 55-kDa proteins was identified through cross-linking experiments and thought to be a strong candidate for the

Injury to Elastin Matrix Contributes to the Pathogenesis of Occlusive Arterial Disease: Therapeutic Implications

Vascular proliferative diseases are a heterogeneous group of disorders including atherosclerosis and coronary restenosis that lead to arterial narrowing and occlusion. Although their etiologies are diverse, these disorders all share common pathologic features including the disruption of elastic fibers and the accumulation of VSMCs within the intima between the endothelium and medial layer of the vessel wall Lusis 2000, Raines and Ross 1993, Sims 2000. A response-to-injury hypothesis has emerged

Conclusions

Elastin matrix is a critical component of the arterial wall with both structural and biologic signaling functions. Current data indicate that elastin is essential during vascular morphogenesis and functions to maintain the homeostasis of the mature vessel wall. The disruption of elastin–VSMC interactions, consequently, is a direct stimulus for the cellular activity leading to occlusive vascular pathology. It is reasonable to speculate that polymorphisms in elastin might contribute to the

Acknowledgements

The authors thank Mary Scriven and Diana Lim for their assistance with preparing figures. In addition, the authors thank David Factor and the Medical Illustrations Department of the Mayo Clinic for the permission to reproduce Figure 3. Research in the authors' laboratory is supported by grants from the National Institutes of Health, American Heart Association, American Cancer Society, the Rockefeller Brothers Fund, a Centers of Excellence award from the State of Utah, and a Technology

References (54)

  • J. Lohler et al.

    Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death

    Cell

    (1984)
  • K.J. Salaymeh et al.

    Evaluation of arterial stiffness in children with Williams syndromedoes it play a role in evolving hypertension?

    Am Heart J

    (2001)
  • F.H. Sims

    The initiation of intimal thickening in human arteries

    Pathology

    (2000)
  • Z. Urban et al.

    Connections between elastin haploinsufficiency and cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome

    Am J Hum Genet

    (2002)
  • J.M. Waugh et al.

    Therapeutic elastase inhibition by alpha-1-antitrypsin gene transfer limits neointima formation in normal rabbits

    J Vasc Interv Radiol

    (2001)
  • M. Yamamoto et al.

    Type I collagen promotes modulation of cultured arterial smooth muscle cells from a contractile to a synthetic phenotype

    Exp Cell Res

    (1993)
  • R.K. Assoian et al.

    The extracellular matrix as a cell cycle control element in atherosclerosis and restenosis

    J Clin Invest

    (1996)
  • A.K. Ewart et al.

    Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene

    J Clin Invest

    (1994)
  • A.K. Ewart et al.

    Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome

    Nat Genet

    (1993)
  • G. Faury et al.

    Relation between outer and luminal diameter in cannulated arteries

    Am J Physiol

    (1999)
  • G. Faury et al.

    Nuclear and cytoplasmic free calcium level changes induced by elastin peptides in human endothelial cells

    Proc Natl Acad Sci USA

    (1998)
  • M.J. Fazio et al.

    Human elastin genenew evidence for localization to the long arm of chromosome 7

    Am J Hum Genet

    (1991)
  • Z.S. Galis et al.

    Matrix metalloproteinases in vascular remodeling and atherogenesisthe good, the bad, and the ugly

    Circ Res

    (2002)
  • C.N. Hahn et al.

    Generalized CNS disease and massive G(M1)-ganglioside accumulation in mice defective in lysosomal acid beta-galactosidase

    Hum Mol Genet

    (1997)
  • U. Hedin et al.

    Control of smooth muscle cell proliferationthe role of the basement membrane

    Thromb Haemost

    (1999)
  • A. Hinek

    Biological roles of the non-integrin elastin/laminin receptor

    Biol Chem

    (1996)
  • A. Hinek et al.

    Impaired elastogenesis in Hurler diseasedermatan sulfate accumulation linked to deficiency in elastin-binding protein and elastic fiber assembly

    Am J Pathol

    (2002)
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