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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1658-1668.)
© 1999 American Heart Association, Inc.

Vascular Biology

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Modulates the Expression of Type VIII Collagen mRNA in Vascular Smooth Muscle Cells and Both Are Codistributed During Atherogenesis

Gabriele Plenz; Stefan Reichenberg; Carsten Koenig; Jürgen Rauterberg; Mario C. Deng; Hideo A. Baba; Horst Robenek

From the Institute for Arteriosclerosis Research, Division of Cell Biology and Ultrastructure Research (G.P., S.R., C.K., J.R., H.R.), and the Departments of Cardiothoracic Surgery (M.C.D.) and Pathology (H.A.B.), Münster, Germany.

Correspondence to Gabriele Plenz, PhD, Institute for Arteriosclerosis Research, Division of Cell Biology and Ultrastructure Research, Domagkstr 3, D-48149 Münster, Germany. E-mail plenz{at}uni-muenster.de

Abstract—The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and type VIII collagen was studied in human arteries. GM-CSF and type VIII collagen were codistributed in all layers of the walls of nondiseased arteries and during early atherogenesis with up to type V lesions. The number of cells expressing both mRNAs increased during the development of advanced atherosclerotic lesions. Whereas type VIII collagen expression increased further in complicated lesions, GM-CSF was downregulated. During early atherogenesis smooth muscle cells (SMC) and endothelial cells were the principal GM-CSF and type VIII collagen mRNA-expressing cell types. In advanced lesions monocytes/macrophages also expressed the mRNAs. In complicated lesions the number of GM-CSF mRNA-expressing SMC was markedly reduced. In in vitro experiments transforming growth factor-ß1, platelet-derived growth factor, and GM-CSF, but not basic fibroblast growth factor, stimulated the expression of type VIII collagen mRNA by SMC. GM-CSF transiently stimulated type VIII collagen transcription. Thus GM-CSF is a prominent component of the regulatory network influencing collagen metabolism during atherogenesis. By modulating the synthesis of type VIII collagen in SMC, GM-CSF may influence the course of plaque development and may govern processes such as cell movement, plaque stability, and thrombus organization.

Key Words: extracellular matrix • remodeling • plaque development • endothelial cells • macrophages

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