Extracellular cathepsins are inhibitors of cellular cholesterol efflux

In atherosclerosis, cholesterol accumulates in intimal macrophages. As the macrophages become cholesterol-loaded, they are converted into foam cells. Indeed, the formation of macrophage foam cells is considered to be a key event in early atherogenesis. Since the ingested cholesterol does not elicit negative feedback regulation of lipoprotein uptake by the macrophages [1], removal of excess cellular cholesterol is of special importance for prevention of foam cell formation. Accordingly, in atherosclerosis, accumulation of cholesterol in macrophages may partially depend on its defective removal by high-density lipoproteins (HDL) [2].