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(Circulation. 2002;105:1830.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Enhanced Expression of the LDL Receptor Family Member LR11 Increases Migration of Smooth Muscle Cells In Vitro

Yanjuan Zhu, MD, PhD; Hideaki Bujo, MD, PhD; Hiroyuki Yamazaki, PhD; Satoshi Hirayama, MD, PhD; Tatsuro Kanaki, PhD; Kazuo Takahashi, MD, PhD; Manabu Shibasaki, PhD; Wolfgang J. Schneider, PhD; Yasushi Saito, MD, PhD

From the Department of Clinical Cell Biology (F5) (Y.Z., S.H., T.K., K.T., M.S., Y.S.) and the Department of Genome Research and Clinical Application (M6) (H.B.), Chiba University Graduate School of Medicine, Chiba, Japan; Kowa Research Institute, Kowa Co Ltd (H.Y.), Tokyo, Japan; and the Department of Molecular Genetics, Biocenter and University of Vienna (S.H., W.J.S), Vienna, Austria.

Correspondence to Dr Hideaki Bujo, Department of Genome Research and Clinical Application (M6), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail hbujo{at}intmed02.m.chiba-u.ac.jp

Background— LR11, a member of the LDL receptor family, is highly expressed in vascular smooth muscle cells (SMCs) of the hyperplastic intima but not media. To further clarify the involvement of LR11 in the process of atherosclerosis, we have characterized the migration and invasion activities of LR11-overexpressing SMCs.

Methods and Results— LR11 cDNA was transfected into the rat SMC line A7r5. Compared with mock cells (C-1), in the presence of platelet-derived growth factor-BB, the transfected cells (R-1 and R-2) showed 3.5- to 4.0-fold higher expression of LR11 protein, 1.7- to 1.8-fold increased migration, and 2.0- to 2.2-fold elevated invasion activities, respectively. The increases were essentially abolished by the addition of receptor-associated protein, anti-LR11 antibodies, or apolipoprotein E. Immunological analyses showed that urokinase-type plasminogen activator receptor (uPAR) levels were increased in LR11-overexpressing cells. Anti–urokinase-type plasminogen activator (uPA) and anti-uPAR antibodies reduced the migration and invasion activities of R-1 and R-2 cells to baseline levels. Receptor-associated protein, anti-LR11 antibodies, and apolipoprotein E decreased uPAR expression in the LR11-overexpressing cells by 50%. Cellular catabolism of uPAR was significantly decreased in R-1 and R-2 cells compared with control. Cultured SMCs isolated from intima of atherosclerotic rabbit aortas showed increased expression levels of LR11 and uPAR and enhanced migration and invasion compared with SMCs from medial layers.

Conclusions— Overexpression of LR11 induces enhanced migration and invasion activities of intimal SMCs in vitro, probably through its regulation of the uPA/uPAR system.

Key Words: atherosclerosis • lipoproteins • receptors • plasminogen

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