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(Circulation Research. 2001;88:2.)
© 2001 American Heart Association, Inc.

Editorials

Extracellular Matrix Remodeling: Multiple Paradigms in Vascular Disease

E. A. Turley

From the Department of Biochemistry/Oncology, University of Western Ontario, London Regional Cancer Centre, London, Ontario, Canada.

Correspondence to E.A. Turley, Department of Biochemistry/Oncology, University of Western Ontario, London Regional Cancer Centre, London, Ontario, Canada. E-mail eva.turley@lrcc.on.ca

Key Words: remodeling • extracellular matrix • Marfan syndrome • CD44 • collagen gel contraction

	Introduction

 
Remodeling of the extracellular matrix is involved in the initiation and progression of a variety of diseases, including cancer¹ and vascular pathology.^{2 3 4 5 6} However, our knowledge of the precise mechanisms that are involved in remodeling processes is still in its infancy. In this issue of Circulation Research, two studies, one by Bunton et al⁷ and one by Travis et al,⁸ provide important examples of the multiplicity and diversity of mechanisms for remodeling that give rise to vascular disease.

Marfan syndrome is a genetic disorder⁹ that results in thin vessel walls. The origin of this disease has been traced to mutations in fibrillin-1, a gene that encodes an extracellular matrix protein that forms microfibrils linking smooth muscle cells to elastin fibrils.¹⁰ Mice homozygous for a targeted hypomorphic allele of fibrillin-1 develop vessel walls with excessive deposition of extracellular matrix elements. Vessels also exhibit elastolysis and intimal hyperplasia.¹¹ Bunton et al⁷ describe a similar sequence of events in patients with Marfan syndrome and, importantly, note that the vessel smooth muscle cells exhibit an abnormal synthetic repertoire, as detected by in situ hybridization and immunochemistry. This includes excessive elastin and matrix metalloproteinase-9 production.¹² This latter collagenase is a known mediator of elastolysis.¹³ Bunton et al⁷ propose a model whereby the loss of normal association with the extracellular matrix forces cells to persistently remodel their extracellular milieu. This promotes fragmentation of the elastin network, causing increased fragility of the vessel wall and eventual death for many patients with Marfan syndrome.

Vessel restenosis remains a . . . [Full Text of this Article]

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