Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport

Reverse cholesterol transport (RCT) is the major protective system against atherosclerosis. In this system, cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of neutral lipids between lipoproteins in plasma. We reported the pathophysiological significance of CETP by clini cal studies with genetic CETP deficiency, showing that this protein plays a crucial role in the RCT system. However, information about the expression of this protein in the initial step of RCT, macrophages (M() in the blood v essels, is still very limited. In the present study, we have performed immu nohistochemical analyses on the expression of CETP in human atherosclerotic lesions. The immunoreactive mass of CETP was abundantly detected in foam c ells in human aortic and coronary atherosclerotic lesions, but not in the n ormal arterial wall. A double immunostaining showed that the majority of CE TP-positive foam cells were derived from M) and a minor population appeared to derive from smooth muscle cells. Transient transfection of CETP cDNA in to COS-7 cells showed that high density lipoprotein (HDL)-mediated efflux o f free cholesterol from the cells expressing CETP was much higher than that from mock-transfected cells, while uptake of HDL-lipids was not affected i n cells transfected with CETP cDNA. Efflux of free cholesterol from the Nl obtained from CETP deficiency was significantly decreased compared with tha t from normal subjects. These data indicate that CETP is expressed in M in the atherosclerotic lesions and may possess an anti-atherogenic function to remove cholesterol from the cells, suggesting another role of CETP at the initial step of RCT. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.