Neointima formation after acute vascular injury. Role of counteradhesive extracellular matrix proteins.
Restenosis currently limits the long-term beneficial effects of balloon coronary angioplasty. Two important cellular events in the development of clinically significant luminal narrowing after angioplasty are 1) increased production of extracellular matrix proteins and 2) acquisition of a motile phenotype by vascular smooth muscle cells. In this paper, smooth muscle cell responses that produce a fibrocellular neointima after acute vascular injury are reviewed. Particular emphasis is placed on specialized extracellular matrix proteins implicated in cell movement and tissue repair. Tenascin and thrombospondin are large, modular extracellular matrix glycoproteins; they possess both adhesive and counteradhesive domains and are expressed at high levels during smooth muscle cell migration and neointima formation after balloon injury to rat carotid artery. The ability of both tenascin and thrombospondin to down-regulate the assembly and activity of focal adhesions (points of cell-extracellular matrix adhesive interactions) may be important in the conversion of stationary, quiescent smooth muscle cells to cells that are able to move and divide within the strongly adhesive vessel wall. Moreover, tenascin is present in the extracellular matrix as a large 6-armed oligomer (a hexabrachion) that contains both cell-binding and matrix protein-binding domains in each of the hexabrachion arms. The large size and multidomain structure of tenascin and thrombospondin suggest that these proteins may be particularly well suited to form a nascent provisional matrix at sites of 1) neointima formation after acute vascular injury, 2) new growth and expansion within primary atherosclerotic plaques, and 3) intimal repair and luminal narrowing in restenosis after angioplasty.
Majesky
M W
MW
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030.
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D019063:Tenascin; D019699:Thrombospondins; D017539:Tunica Intima / Q000502:physiology*
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D019063:Tenascin; D019699:Thrombospondins