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(Circulation. 2001;104:1407.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Apolipoprotein J/Clusterin Is Induced in Vascular Smooth Muscle Cells After Vascular Injury

Masaaki Miyata, MD, PhD; Sadatoshi Biro, MD, PhD; Hiroshi Kaieda, MD, PhD; Hideyuki Eto, MD; Koji Orihara, MD; Takashi Kihara, MD; Hachiro Obata, MD, PhD; Noriko Matsushita, PhD; Takami Matsuyama, MD, PhD; Chuwa Tei, MD, PhD

From the First Department of Internal Medicine (M.M., S.B., H.K., H.E., K.O., T.K., H.O., C.T.) and Medical Zoology and Immunology (N.M., T.M.), Faculty of Medicine, Kagoshima University, Kagoshima, Japan.

Correspondence to Sadatoshi Biro, MD, PhD, First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. E-mail biro{at}m2.kufm.kagoshima-u.ac.jp

Background—— Understanding the precise molecular mechanisms underlying the phenomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to identify the genes involved in vascular restenosis.

Methods and Results—— Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apolipoprotein J (apoJ)/clusterin, were constitutively expressed in noninjured aorta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, and returned to the control level at 24 weeks. Western blot and immunohistochemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55-fold increase) at 2 to 8 weeks. The expression of apoJ protein continued until 24 weeks after injury. In situ hybridization revealed that apoJ mRNA was expressed in smooth muscle cells (SMCs) of media at 2 days after injury and in SMCs of media and neointima at 2 weeks. To analyze the function of apoJ, stably transfected rabbit SMCs were created. The expression of apoJ stimulated proliferation and migration of SMCs.

Conclusions—— ApoJ is dramatically induced in media and neointima after vascular injury, suggesting that apoJ contributes to restenosis after angioplasty.

Key Words: angioplasty • restenosis • muscle, smooth • apolipoproteins

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