The evil in atherosclerosis: adherent platelets induce foam cell formation.
Platelet interaction with circulating progenitor cells plays an important role for repair mechanisms at sites of vascular lesions. Foam cell formation represents a key process in atherosclerotic plaque formation. We revealed that platelets regulate recruitment and differentiation of CD34 (+) progenitor cells into foam cells and endothelial cells. Adhesion studies showed that platelets recruit CD34 (+) progenitor cells via specific adhesion receptors, including P-selection/P-selectin glycoprotein ligand 1, and beta (1) and beta (2) integrins. CD34 (+) progenitor cells were coincubated with human platelets for 1 week. We demonstrated that a substantial number of CD34 (+) cells differentiated into foam cells. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and agonists of peroxisome proliferator-activated receptor-alpha and -gamma (PPAR-alpha and -gamma agonists) reduced this foam cell generation via inhibition of matrix metalloproteinase 9 secretions. Foam cell formation is also induced by low-density lipoproteins (LDLs). It was revealed that platelets take up modified LDL (fluorochrome-conjugated acetylated LDL) that is stored in the dense granules and internalized rapidly into the foam cells. These findings emphasize that the balance between endothelial cell regeneration and platelet-mediated foam cell generation derived from CD34 (+) progenitor cells may play a critical role in atherogenesis and atheroprogression.
Daub
Karin
K
Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany.
Lindemann
Stephan
S
Langer
Harald
H
Seizer
Peter
P
Stellos
Konstantinos
K
Siegel-Axel
Dorothea
D
Gawaz
Meinrad
M
D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D005487:Foam Cells / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D010973:Platelet Adhesiveness / Q000502:physiology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047492:Peroxisome Proliferator-Activated Receptors