Chlamydia pneumoniae induces macrophage-derived foam cell formation by up-regulating acyl-coenzyme A: cholesterol acyltransferase 1

Abstract

In macrophages, the accumulation of cholesteryl esters synthesized by acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) plays a crucial role in foam cell formation, a hallmark of early atherosclerotic lesions. It is suggested that Chlamydia pneumoniae ( C. pneumoniae) induces foam cell formation. However, the mechanism of foam cell formation induced by C. pneumoniae has not been fully elucidated. In this study, we found that C. pneumoniae increased the expression of acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) mRNA and protein in a dose-dependent manner in THP-1-derived macrophages exposed to low density lipoprotein (LDL). In addition, C. pneumoniae dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPAR γ) mRNA and protein. Rosiglitazone, a specific PPAR γ agonist, not only dose-dependently alleviated the down-regulation of PPAR γ expression by C. pneumoniae infection, but also dose-dependently inhibited the C. pneumoniae-induced ACAT1 expression. Furthermore, higher doses of rosiglitazone (10 and 20 μM) suppressed the C. pneumoniae-induced foam cell formation from morphological (Oil red O staining) and biochemical (zymochemistry method) criteria. These results first demonstrate that C. pneumoniae induces macrophage-derived foam cell formation by up-regulating ACAT1 expression via PPAR γ-dependent pathway, which may contribute to its pro-atherogenic properties.