ABSTRACT
A variety o f matrix proteins are implicated in the pathogenesis o f chronic allograft vascular disease including fibronectin, tenascin, collagen, glycosaminoglycans and proteoglycans. Alter ations in these matrix components can influ ence a range of cellular functions including proliferation, migration, differentiation, adhesion and apoptosis. Our laboratory has shown that central to the pathobiology of allograft vascular disease, there is an increase in synthesis and secretion of the extracellular matrix glycoprotein fibronectin in response to cytokines and liberation o f proteolytic enzymes, specifically elastases. Fibronectin creates a two-way highway, both encourag ing the transendothelial migration of inflam matory cells and promoting smooth muscle cell migration into the subendothelium. Elastases also release mitogenically active growth factors from proteoglycan stores and upregulate the glycoprotein tenascin, which plays a critical role in amplifying the prolif erative response of the vascular smooth muscle cells to mitogens. The following is a discus sion of the mechanisms which lead to changes in fibronectin and tenascin and studies which support their critical roles in SMC migration and proliferation, related to occlusive changes in coronary arteries following placement of a cardiac allograft.
