New mechanism for foam cell generation in atherosclerotic lesions.

Abstract

Because of a close association between platelets and macrophages in early fatty streak lesions, the hypothesis was tested that platelets contribute to lesion progression by directly enhancing macrophage cholesteryl ester (CE)

Absence of P-selectin delays fatty streak formation in mice.

“…This interaction could bring platelets, with all of their biological activities, into the lesion (2,48). Furthermore, platelets can contribute cholesterol esters to macrophages (49,50). Thus it is possible that endothelial P-selectin is responsible for the adhesion of monocytes to the lesion site, whereas platelet P-selectin may contribute to cholesterol accumulation in macrophages in situ.…”

Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils. Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo.

“…Potent suppression by apo E of lymphocyte activation by mitogens and antigens is also well recognized (20)(21)(22)(23), and emphasizes that apo E can possess tissue-specific paracrine functions (48). Apo E secretion from monocyte/macrophages is increased by cholesterol loading (49), suggesting the possibility that synovial apo E production could be enhanced by the exposure of these cells to cellular debris, platelets (50), and intraarticular, oxidized LDL (51). Importantly, macrophage apo E secretion is suppressed by endotoxin (52) and certain particulates (53), suggesting that modulation of apo E secretion is one mechanism for macrophages to relate their state of activation to neighboring lymphocytes (14,22).…”

Participation of macrophages in atherosclerotic lesion morphology in LDLr−/− mice

“…Adherent cells were extracted at 1 ml/well for 30 min into hexane-isopropanol (3:2). The lipid extracts were removed from the well, dried down in glass tubes, and stored at Ϫ 20 Њ C for further lipid analysis by thin layer chromatography as described previously (15). After lipid extraction, cells were lysed for 30 min with 0.1 N NaOH at 0.5 ml/well.…”