TY - JOUR
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
N1 - Funding Information:
This work was supported by the research grants from Sasagawa Foundation and Uehara Memorial Foundation to Z. Zhang. This work was supported by grants-in-aid to S. Yamashita (No. 11557055 and No. 10671070) and to N. Sakai (No. 11557054 and No. 10671067) from the Ministry of Education, Science, Sports, and Culture of Japan. This work was supported by research grants from Study Group of Molecular Cardiology (Japan), from Osaka Heart Club (Japan), from Japan Heart Foundation (Japan), from Japan Heart Foundation/Pfizer Grant for Research on Hypertension and Vascular Metabolism (Japan), and from Tanabe Medical Frontier Conference (TMFC; Japan) to K. Hirano. This work was supported by a research grant from JSPS-RFTF97L00801 to Y. Matsuzawa. We thank Professor Keizo Inoue (Tokyo University, Japan) for providing the antibody against human CETP. We thank Mr. Yoshito Komatsu (JT Central Pharmaceutical Research Institute) for helping with the cholesterol uptake assay and providing the neutralizing antibody against CETP. We thank Mrs. Makoto Nagano and Tohru Egashira (BML, Saitama, Japan) for measuring the protein mass of CETP and providing the recombinant CETP. We thank Ms. Katsumi Yamamori and Ms. Chiaki Ikegami for their skillful technical assistance.
PY - 2001
Y1 - 2001
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.
AB - 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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U2 - 10.1016/S0021-9150(01)00490-7
DO - 10.1016/S0021-9150(01)00490-7
M3 - Article
C2 - 11689208
AN - SCOPUS:0034751739
SN - 0021-9150
VL - 159
SP - 67
EP - 75
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -