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Platelets induce differentiation of human CD34 + progenitor cells into foam cells and endothelial cells
Author(s) -
Daub Karin,
Langer Harald,
Seizer Peter,
Stellos Konstantinos,
May Andreas E.,
Goyal Pankaj,
Bigalke Boris,
Schönberger Tanja,
Geisler Tobias,
SiegelAxel Dorothea,
J. Oostendorp Robert A.,
Lindemann Stephan,
Gawaz Meinrad
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6265fje
Subject(s) - progenitor cell , microbiology and biotechnology , endothelial stem cell , cd34 , stem cell , platelet , chemistry , homing (biology) , cellular differentiation , biology , immunology , biochemistry , in vitro , ecology , gene
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 β 1 ‐ and β 2 ‐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 metallo‐proteinase‐9 (MMP‐9) secretion. Finally, agonists of peroxisome proliferator‐activated receptor‐α and ‐γ 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. FASEB J. 20, E1935–E1944 (2006)