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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:67.)
© 2004 American Heart Association, Inc.

Vascular Biology

Overexpression of Decorin by Rat Arterial Smooth Muscle Cells Enhances Contraction of Type I Collagen In Vitro

Hannu Järveläinen; Robert B. Vernon; Michel D. Gooden; Aleksandar Francki; Stephanie Lara; Pamela Y. Johnson; Michael G. Kinsella; E. Helene Sage; Thomas N. Wight

From the Departments of Medicine and Medical Biochemistry, University of Turku (H.J.), Turku, Finland; Department of Vascular Biology, The Hope Heart Institute (H.J., R.B.V., M.D.G., A.F., P.Y.J., M.G.K., E.H.S., T.N.W.), Seattle, WA; Department of Pathology, University of Washington (S.L.), Seattle, WA.

Correspondence to Thomas N. Wight, PhD, The Hope Heart Institute, Seattle Life Science Center, Suite 783, 1124 Columbia St, Seattle, WA 98104. E-mail twight{at}hopeheart.org

Objective— Overexpression of decorin reduces neointimal thickening in balloon-injured carotid arteries of rats by decreasing the volume of neointimal extracellular matrix (ECM). We examined the hypothesis that decorin regulates ECM volume by stimulating cell-mediated contraction of collagen-rich ECMs.

Methods and Results— Rat arterial smooth muscle cells (ASMCs) transduced with bovine decorin cDNA by retroviral transfection (LDSN) exhibited enhanced contraction of collagen gels in vitro when compared with vector-only transduced (LXSN) cells. Addition of recombinant decorin to LXSN or LDSN cells did not stimulate contraction of collagen gels. Enhanced contraction of collagen by LDSN cells was unaffected by the metalloproteinase inhibitor GM6001. LDSN cells exhibited increased expression of type I collagen mRNA when compared with that of LXSN cells. Correspondingly, collagen gel contraction by LDSN cells was reduced by inhibition of collagen synthesis by 3,4-L-dehydroproline (L-DHP). Antibodies to 1ß1-integrin, but not to 2ß1-integrin, blocked collagen contraction by both LXSN and LDSN cells. However, LXSN and LDSN cells expressed similar levels of 1- and ß1-integrin mRNAs.

Conclusions— Decorin synthesized de novo by ASMCs increases type I collagen synthesis and enhances contraction of collagen gels. Regulated synthesis of decorin may be a useful therapeutic approach to reduce ECM volume in vascular disease.

Key Words: extracellular matrix • decorin • collagen, type I • muscle, smooth • integrin

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