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 β₁ and β₂ 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-α and -γ (PPAR-α and -γ 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.

KEYWORDS

Platelets - atherothrombosis - foam cells - vascular lesions - endothelium - progenitor cells

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