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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:2049.)
© 2002 American Heart Association, Inc.

Atherosclerosis

Expression of G2A, a Receptor for Lysophosphatidylcholine, by Macrophages in Murine, Rabbit, and Human Atherosclerotic Plaques

Yoshiyuki Rikitake; Ken-ichi Hirata; Tomoya Yamashita; Kenji Iwai; Seiichi Kobayashi; Hiroshi Itoh; Masanori Ozaki; Junya Ejiri; Masashi Shiomi; Nobutaka Inoue; Seinosuke Kawashima; Mitsuhiro Yokoyama

From the Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine (Y.R., K.H., T.Y., K.I., M.O., J.E., N.I., S. Kawashima, M.Y.) and Department of Surgical Pathology (S. Kobayashi, H.I.), Kobe University Graduate School of Medicine, and the Institute for Experimental Animals (M.S.), Kobe University School of Medicine, Kobe, Japan.

Correspondence to Mitsuhiro Yokoyama, MD, PhD, Professor, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. E-mail yokoyama{at}med.kobe-u.ac.jp

Abstract

Objective— Lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low density lipoprotein, has been demonstrated to induce multiple functional alterations of vasculature that are potentially involved in atherosclerosis. Recently, an orphan G-protein-coupled receptor, G2A, has been identified as a high-affinity receptor for LPC. Although it has been demonstrated that G2A is expressed predominantly in lymphoid tissues and lymphocytes, there are no reports to determine whether G2A is expressed in atherosclerotic lesions and cardiovascular cells.

Methods and Results— Immunohistochemistry with an anti-G2A antibody revealed that G2A was expressed predominantly by macrophages within atherosclerotic lesions at the aortic root of apolipoprotein E-deficient mice and the thoracic aortas of Watanabe heritable hyperlipidemic rabbits. In atherosclerotic plaques of human coronary arterial specimens, G2A was expressed by macrophages within the lipid-rich plaques, whereas no immunoreactivity of G2A was observed in fibrous plaques where macrophages did not exist. Reverse transcription-polymerase chain reaction analysis demonstrated that G2A mRNA was highly expressed in human and murine monocytes/macrophages. The expression of G2A protein was detected in human and murine monocytes/macrophages by immunoblotting.

Conclusions— These findings demonstrate that monocytes/macrophages abundantly express G2A and suggest that G2A may play a role in the formation and progression of atherosclerotic lesions.

Key Words: atherosclerosis • lipids • plaque • receptors

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