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Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:622-627
Published online before print December 29, 2004, doi: 10.1161/01.ATV.0000154489.53077.4e
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:622.)
© 2005 American Heart Association, Inc.


Atherosclerosis and Lipoproteins

Expression of the LXR{alpha} Protein in Human Atherosclerotic Lesions

Yuichiro Watanabe; Shuying Jiang; Wakako Takabe; Riuko Ohashi; Toshiya Tanaka; Yasutoshi Uchiyama; Keiko Katsumi; Hiroko Iwanari; Noriko Noguchi; Makoto Naito; Takao Hamakubo; Tatsuhiko Kodama

From the Department of Systems Biology and Medicine (Y.W., W.T., T.T., N.N., T.H., T.K.), Research Center for Advanced Science and Technology, the University of Tokyo; the Immunology Research Department (Y.W.), Tokyo New Drug Research Laboratories II, Pharmaceutical Division, Kowa Co Ltd; Perseus Proteomics Inc (S.J., Y.U., K.K., H.I.), Tokyo; and the Department of Cellular Function (S.J., R.O., M.N.), Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Correspondence to Tatsuhiko Kodama, Laboratory for Systems Biology and Medicine at RCAST #34, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan. E-mail kodama{at}lsbm.org

Objective— Liver X–activated receptor {alpha} (LXR{alpha}) regulates multiple genes controlling cholesterol metabolism and transport. To clarify its role in atherogenesis, we established a monoclonal antibody recognizing native human LXR{alpha} protein and studied the expression pattern in human atherosclerotic lesions.

Methods and Results— A novel monoclonal antibody PPZ0412 was raised against the ligand-binding domain of LXR{alpha}, which can be used for immunostaining of human LXR{alpha} protein. LXR{alpha} protein was detected in the nucleus of macrophages in the liver, spleen, or lung and also in hepatocytes and adipocytes. In atherosclerotic lesions, the LXR{alpha} protein was detected in macrophages positive for scavenger receptor class A and/or CD68.

Conclusions— In the human body, the LXR{alpha} protein is highly expressed in macrophage lineage cells and foam cells in atherosclerotic lesions and is identified as a target for intervention in atherosclerotic disease.

We established the monoclonal antibody recognizing native human LXR{alpha} protein PPZ0412 and studied the expression of LXR{alpha} protein. In the human body, the LXR{alpha} protein is highly expressed in macrophage lineage and atherosclerotic lesion foam cells and is identified as a target for intervention in atherosclerotic disease.


Key Words: LXR{alpha} • atherosclerosis • macrophages • monoclonal antibody




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