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Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice

GABRIELE PLENZ^*,,,1, HEIKE ESCHERT^*,, STEFAN BEISSERT, VOLKER ARPS^*, JÜRGEN R. SINDERMANN^*,, HORST ROBENEK^* and WOLFGANG VÖLKER^*

^* Institute for Arteriosclerosis Research, 48149 Münster, Germany;
Department of Cardiology and Angiology,
Department of Thoracic and Cardiovascular Surgery, University Hospital Münster, 48149 Münster, Germany; and
Department of Dermatology, University Hospital Münster, 48149 Münster, Germany

¹Correspondence: Institute for Arteriosclerosis Research, Domagkstr. 3, D-48149 Münster, Germany. E-mail: plenz{at}uni-muenster.de

GM-CSF takes part in the cytokine network regulating the metabolism of extracellular matrix (ECM) during atherogenesis. Since data also point to an effect of GM-CSF on the vascular ECM in general, the vascular collagenous matrix was studied in wild-type and GM-CSF-deficient mice. Histological examination revealed a disorganized vascular ECM in GM-CSF-deficient mice involving the collagenous matrix and elastic fiber system. As shown by electron microscopy, collagen bundles were disrupted and reduced. The diameter of fibrils varied widely. mRNA expression of collagens and related molecules was studied. Fibrillar collagens were markedly reduced, 1(I)procollagen to 16.5% of control levels 1(III)procollagen was abolished whereas the expression level of network-forming 1(VIII)procollagen was not altered. As shown by in situ hybridization, the number of collagen-expressing cells was reduced. Matrix metalloproteinases and their inhibitor 1 were not affected by GM-CSF deficiency. Our studies demonstrate that GM-CSF plays a major role in the cytokine network regulating the metabolism of vascular collagens. GM-CSF deficiency leads to an altered composition of the vascular collagenous matrix, i.e., reduced amount of fibrillar collagen, altered ratio of fibrillar and network-forming collagen, and failures in the fibrillogenesis. We suggest that GM-CSF is a basic requirement for the maintenance of vessel wall integrity and resilience.—Plenz, G., Eschert, H., Beissert, S., Arps, V., Sindermann, J. R., Robenek, H., Völker, W. Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice.

Key Words: GM-CSF deficiency • vascular collagens • remodeling • atherogenesis

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