CD36 and Macrophage Scavenger Receptor A Modulate Foam Cell Formation via Inhibition of Lipid-Laden Platelet Phagocytosis

ABSTRACT

CD34⁺ progenitor cells are a promising source of regeneration in atherosclerosis or ischemic heart disease. However, as recently published, CD34⁺ progenitor cells have the potential to differentiate not only into endothelial cells but also into foam cells upon interaction with platelets. The mechanism of platelet-induced differentiation of progenitor cells into foam cells is as yet unclear. In the present study we investigated the role of scavenger receptor (SR)-A and CD36 in platelet-induced foam cell formation. Human CD34⁺ progenitor cells were freshly derived from human umbilical veins and were co-incubated with platelets (2 × 10⁸/mL) up to 14 days resulting in large lipid-laden foam cells. Developing macrophages expressed SR-A, CD36, and Lox-1 as measured by fluorescent-activated cell sorting analysis. The presence of a blocking anti-CD36 or anti-SR-A antibody nearly abrogated foam cell formation, whereas anti-Lox-1 did not affect foam cell formation. Consistently blocking either anti-CD36 or anti-SR-A antibody significantly reduced the phagocytosis of lipid-laden platelets by macrophages. We conclude that CD36 and SR-A play an important role in platelet-induced foam cell formation from CD34⁺ progenitor cells and thus represent a promising target to inhibit platelet-induced foam cell formation.

Progenitor cells - platelets - foam cells - CD36 - SR-A

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