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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalAtherosclerosis
Volume159
Issue number1
DOIs
Publication statusPublished - 10-11-2001

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Cholesterol Ester Transfer Proteins
Cholesterol
Foam Cells
HDL Lipoproteins
Complementary DNA
Lipids
COS Cells
Lipoproteins
Smooth Muscle Myocytes
Transfection
Blood Vessels
Atherosclerosis
Proteins
Macrophages

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Zhang, Zhongyan ; Yamashita, Shizuya ; Hirano, Ken ichi ; Nakagawa-Toyama, Yumiko ; Matsuyama, Akifumi ; Nishida, Makoto ; Sakai, Naohiko ; Fukasawa, Masayoshi ; Arai, Hiroyuki ; Miyagawa, Jun ichiro ; Matsuzawa, Yuji. / Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport. In: Atherosclerosis. 2001 ; Vol. 159, No. 1. pp. 67-75.
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abstract = "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.",
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Zhang, Z, Yamashita, S, Hirano, KI, Nakagawa-Toyama, Y, Matsuyama, A, Nishida, M, Sakai, N, Fukasawa, M, Arai, H, Miyagawa, JI & Matsuzawa, Y 2001, 'Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport', Atherosclerosis, vol. 159, no. 1, pp. 67-75. https://doi.org/10.1016/S0021-9150(01)00490-7

Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport. / Zhang, Zhongyan; Yamashita, Shizuya; Hirano, Ken ichi; Nakagawa-Toyama, Yumiko; Matsuyama, Akifumi; Nishida, Makoto; Sakai, Naohiko; Fukasawa, Masayoshi; Arai, Hiroyuki; Miyagawa, Jun ichiro; Matsuzawa, Yuji.

In: Atherosclerosis, Vol. 159, No. 1, 10.11.2001, p. 67-75.

Research output: Contribution to journalArticle

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T1 - Expression of cholesteryl ester transfer protein in human atherosclerotic lesions and its implication in reverse cholesterol transport

AU - Zhang, Zhongyan

AU - Yamashita, Shizuya

AU - Hirano, Ken ichi

AU - Nakagawa-Toyama, Yumiko

AU - Matsuyama, Akifumi

AU - Nishida, Makoto

AU - Sakai, Naohiko

AU - Fukasawa, Masayoshi

AU - Arai, Hiroyuki

AU - Miyagawa, Jun ichiro

AU - Matsuzawa, Yuji

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N2 - 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.

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