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

Zhongyan Zhang, Shizuya Yamashita, Ken ichi Hirano, Yumiko Nakagawa-Toyama, Akifumi Matsuyama, Makoto Nishida, Naohiko Sakai, Masayoshi Fukasawa, Hiroyuki Arai, Jun ichiro Miyagawa, Yuji Matsuzawa

研究成果: Article

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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 clinical 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 (Mφ) in the blood vessels, is still very limited. In the present study, we have performed immunohistochemical analyses on the expression of CETP in human atherosclerotic lesions. The immunoreactive mass of CETP was abundantly detected in foam cells in human aortic and coronary atherosclerotic lesions, but not in the normal arterial wall. A double immunostaining showed that the majority of CETP-positive foam cells were derived from Mφ and a minor population appeared to derive from smooth muscle cells. Transient transfection of CETP cDNA into COS-7 cells showed that high density lipoprotein (HDL)-mediated efflux of free cholesterol from the cells expressing CETP was much higher than that from mock-transfected cells, while uptake of HDL-lipids was not affected in cells transfected with CETP cDNA. Efflux of free cholesterol from the Mφ obtained from CETP deficiency was significantly decreased compared with that from normal subjects. These data indicate that CETP is expressed in Mφ 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.

元の言語English
ページ(範囲)67-75
ページ数9
ジャーナルAtherosclerosis
159
発行部数1
DOI
出版物ステータスPublished - 2001

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Zhang, Z., Yamashita, S., Hirano, K. I., Nakagawa-Toyama, Y., Matsuyama, A., Nishida, M., Sakai, N., Fukasawa, M., Arai, H., Miyagawa, J. I., & Matsuzawa, Y. (2001). Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport. Atherosclerosis, 159(1), 67-75. https://doi.org/10.1016/S0021-9150(01)00490-7