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Platelets induce differentiation of human CD34⁺ progenitor cells into foam cells and endothelial cells

Karin Daub^*, Harald Langer^*, Peter Seizer^*, Konstantinos Stellos^*, Andreas E. May^*, Pankaj Goyal, Boris Bigalke^*, Tanja Schönberger^*, Tobias Geisler^*, Dorothea Siegel-Axel^*, Robert A. J. Oostendorp, Stephan Lindemann^* and Meinrad Gawaz^*,1

^* Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany;

Institute for Prevention of Cardiovascular Diseases, University of Munich, Munich, Germany; and

Medizinische Klinik III, Klinikum rechts der Isar München, Technische Universität, Munich, Germany

¹Correspondence: Medizinische Klinik III, Universitätsklinikum Tübingen, Otfried-Müller Str.10, 72076 Tübingen, Germany. E-mail: meinrad.gawaz{at}med.uni-tuebingen.de

ABSTRACT

Recruitment of human CD34⁺ progenitor cells toward vascular lesions and differentiation into vascular cells has been regarded as a critical initial step in atherosclerosis. Previously we found that adherent platelets represent potential mediators of progenitor cell homing besides their role in thrombus formation. On the other hand, foam cell formation represents a key process in atherosclerotic plaque formation. To investigate whether platelets are involved in progenitor cell recruitment and differentiation into endothelial cells and foam cells, we examined the interactions of platelets and CD34⁺ progenitor cells. Cocultivation experiments showed that human platelets recruit CD34⁺ progenitor cells via the specific adhesion receptors P-selectin/PSGL-1 and ß₁- and ß₂-integrins. Furthermore, platelets were found to induce differentiation of CD34⁺ progenitor cells into mature foam cells and endothelial cells. Platelet-induced foam cell generation could be prevented partially by HMG coenzyme A reductase inhibitors via reduction of matrix metalloproteinase-9 (MMP-9) secretion. Finally, agonists of peroxisome proliferator-activated receptor- and - attenuated platelet-induced foam cell generation and production of MMP-9. The present study describes a potentially important mechanism of platelet-induced foam cell formation and generation of endothelium in atherogenesis and atheroprogression. The understanding and modulation of these mechanisms may offer new treatment strategies for patients at high risk for atherosclerotic diseases.—Daub, K., Langer, H., Seizer, P., Stellos, K., May, A. E., Goyal, P., Bigalke, B., Schönberger, T., Geisler, T., Siegel-Axel, D., Oostendorp, R. A. J., Lindemann, S., Gawaz, M. Platelets induce differentiation of human CD34⁺ progenitor cells into foam cells and endothelial cells.

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