NEOINTIMA FORMATION AFTER ACUTE VASCULAR INJURY - ROLE OF COUNTERADHESIVE EXTRACELLULAR-MATRIX PROTEINS

Restenosis currently limits the long-term beneficial effects of balloo n coronary angioplasty. Two important cellular events in the developme nt of clinically significant luminal narrowing after angioplasty are 1 ) increased production of extracellular matrix proteins and 2) acquisi tion of a motile phenotype by vascular smooth muscle cells. In this pa per smooth muscle cell responses that produce a fibrocellular neointim a after acute vascular injury are reviewed. Particular emphasis is pla ced on specialized extracellular matrix proteins implicated in cell mo vement and tissue repair. Tenascin and thrombospondin are large, modul ar 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 t o down-regulate the assembly and activity of focal adhesions (points o f 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 w all. Moreover tenascin is present in the extracellular matrix as a lar ge 6-armed oligomer (a hexabrachion) that contains both cell-binding a nd matrix protein-binding domains in each of the hexabrachion arms. Th e 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 ac ute vascular injury, 2) new growth and expansion within primary athero sclerotic plaques, and 3) intimal repair and luminal narrowing in rest enosis after angioplasty.