Intracellular lipids and inflammatory activity in macrophage foam cells

Cardiovascular disease (CVD) is characterized by lipid accumulation and inflammation in arteries. The disease starts early in life with migration of monocytes into the arterial wall where they engulf entrapped lipoproteins and become macrophage foam cell. A simultaneous inflammatory response further enhances lipid and cell accumulation at sites of lesion development, resulting in progression of atherosclerotic plaque formation. The present investigation aimed at providing further information on the effects of foam cell formation on inflammation and intracellular lipid accumulation, with special interest in lipid accumulation during and after macrophage uptake of non-oxidized lipoproteins. Our data demonstrates that lipoprotein-induced foam cell formation results in patterns of cytokine release specific for lipoprotein species, patterns that are overruled by activation of foam cells with exogenous tumour necrosis factor-a (TNF-a). Furthermore the pro-inflammatory cytokines interleukin-1? and TNF-a affect foam cell intracellular lipid metabolism, resulting in decreased utilization of stored lipids and further promotion of foam cell formation. Finally, expression of lipid droplet-associated proteins was studied in relation to foam cell formation. Perilipin negatively correlated with intracellular lipid levels, with an increasing adipophilin-to-perilipin ratio in lipid loaded cells. As these proteins may be functionally important with regard to intracellular lipid droplet stability, by steric effects or by contributing to lipid hydrolysis, the relative protein ratio could play an important role in foam cell lipid metabolism. With foam cells being key participants in development of CVD, insight in how lipid droplet-associated proteins and inflammation affect lipid turnover may provide tools for control of foam cell formation in atherosclerotic plaques