title: The evil in atherosclerosis: adherent platelets induce foam cell formation.
abstract: 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.
authors.affiliation: Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Daub
authors.forename: Stephan
authors.initials: S
authors.lastname: Lindemann
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Dorothea
authors.initials: D
authors.lastname: Siegel-Axel
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: 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*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047492:Peroxisome Proliferator-Activated Receptors