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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1356.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Syndecan-1

An Inhibitor of Arterial Smooth Muscle Cell Growth and Intimal Hyperplasia

Nozomi Fukai; Richard D. Kenagy; Lihua Chen; Lu Gao; Guenter Daum; Alexander W. Clowes

From the Department of Surgery and Center for Cardiovascular Biology (N.F., R.D.K., L.G., L.C., G.D., A.W.C.) and the Department of Biochemistry (G.D.), University of Washington, Seattle.

Correspondence to Alexander W. Clowes, MD, Department of Surgery, University of Washington, 1959 NE Pacific Street, Box 356410, Seattle, WA 98195-6410. E-mail clowes{at}u.washington.edu or Nozomi Fukai, Kashiwa City Hospital, 1-3 Fuse, Kashiwa-shi, Chiba 277-0825, Japan.

Objective— Arterial injury induces smooth muscle cell (SMC) proliferation, migration, and intimal accumulation of cells and extracellular matrix. These processes are regulated by the administration of the glycosaminoglycans heparin and heparan sulfate, but little is known about the role of endogenous heparan sulfate proteoglycans in the vessel wall. We investigated the response to carotid injury of syndecan-1–null mice to assess the function of one of a conserved family of transmembrane heparan and chondroitin sulfate proteoglycans.

Methods and Results— Syndecan-1–null mice developed a large neointimal lesion after injury, whereas wild-type mice made little or none. This was accompanied by a significant increase in both medial and intimal SMC replication. Cultured syndecan-1–null SMCs showed a significant increase in proliferation in response to PDGF-BB, thrombin, FGF2, EGF, and serum. In response to thrombin, PDGF-BB, and serum syndecan-1–null SMCs expressed more PDGF-B chain message than did wild-type SMCs. Downregulation of PDGF-BB or PDGFRβ inhibited thrombin-, PDGF-BB–, and serum-induced DNA synthesis in syndecan-1–null SMCs.

Conclusions— These results suggest the possibility that syndecan-1 may limit intimal thickening in injured arteries by suppressing SMC activation through inhibition of SMC PDGF-B chain expression and PDGFRβ activation.

Key Words: syndecan • platelet-derived growth factor • smooth muscle • arterial injury