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

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 arte ries and during early atherogenesis with up to type V lesions. The number o f cells expressing both mRNAs increased during the development of advanced atherosclerotic lesions. Whereas type VIII collagen expression increased fu rther in complicated lesions, GM-CSF was downregulated. During early athero genesis smooth muscle cells (SMC) and endothelial cells were the principal GM-CSF and type VIII collagen mRNA-expressing cell types. In advanced lesio ns monocytes/macrophages also expressed the mRNAs. In complicated lesions t he number of GM-CSF mRNA-expressing SMC was markedly reduced. In in vitro e xperiments transforming growth factor-beta 1, platelet-derived growth facto r, and GM-CSF, but not basic fibroblast growth factor, stimulated the expre ssion of type VIII collagen mRNA by SMC. GM-CSF transiently, stimulated typ e 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 influenc e the course of plaque development and may govern processes such as cell mo vement, plaque stability, and thrombus organization.