ROLE OF CD44 IN THE REACTION OF VASCULAR SMOOTH-MUSCLE CELLS TO ARTERIAL-WALL INJURY

CD44, the principal receptor for hyaluronic acid, is a widely distribu ted cell surface proteoglycan involved in cellular activation, prolife ration, and migration. These processes are also central to the vascula r smooth muscle cell's response to arterial wall injury. We evaluated the expression of CD44 and its isoform, CD44-v6, on vascular smooth mu scle cells in vitro and in vivo and assessed the role of CD44 in DNA s ynthesis. Cultured vascular smooth muscle cells expressed CD44 and CD4 4-v6 at levels equal to or higher than those of the beta(1) and beta(3 ) integrins. In a rat carotid artery balloon injury model, CD44 and CD 44-v6 mRNAs were upregulated in vascular smooth muscle cells after inj ury, and CD44 protein expression was greatest at the luminal edge of t he growing neointima, CD44-expressing smooth muscle cells proliferated actively, and hyaluronic acid expression increased after injury in a temporal pattern similar to that of CD44. Through binding to hyaluroni c acid, CD44 augmented DNA synthesis in cultured human and rat smooth muscle cells by 48+/-7.8 and 100+/-12.5%, respectively, an effect inhi bited by an anti-CD44 antibody that blocked hyaluronate binding. These observations support a role for CD44 in the reaction of vascular smoo th muscle cells to arterial wall injury.