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(Circulation. 2000;102:2528.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Regulated Expression of the BTEB2 Transcription Factor in Vascular Smooth Muscle Cells

Analysis of Developmental and Pathological Expression Profiles Shows Implications as a Predictive Factor for Restenosis

Yoichi Hoshino, MD; Masahiko Kurabayashi, MD; Tsugiyasu Kanda, MD; Akira Hasegawa, MD; Hironosuke Sakamoto, MD; Ei-ichi Okamoto, MD; Keiko Kowase, MD; Noboru Watanabe, MD; Ichiro Manabe, MD; Toru Suzuki, MD; Akihiko Nakano, MD; Shin-ichi Takase, MD; Josiah N. Wilcox, PhD; Ryozo Nagai, MD

From the Second Department of Internal Medicine, Gunma University School of Medicine (Y.H., M.K., T.K., A.H., H.S., K.K.), and the Department of Cardiovascular Medicine, Saiseikai Maebashi Hospital (A.N., S.T.), Gunma; the First Department of Internal Medicine, Shinsyu University School of Medicine, Nagano (N.W.); and the Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo (I.M., T.S., R.N.), Japan; and the Department of Medicine, Emory University, Atlanta, Ga (E.O., J.N.W.)

Correspondence to Ryozo Nagai, MD, The Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail nagai-tky{at}umin.ac.jp

Background—We have previously shown BTEB2, a Krüppel-like zinc finger transcription factor, to regulate expression of the SMemb/NMHC-B gene, which has been implicated in phenotypic modulation of smooth muscle cells (SMCs). The present study was done to assess the developmental and pathological expression profiles of BTEB2 and to further evaluate the clinical relevance of BTEB2 expression in human coronary artery disease.

Methods and Results—Immunohistochemistry showed developmentally regulated expression of BTEB2 with abundant expression in fetal but not in adult aortic SMCs of humans and rabbits. In balloon-injured aortas, predominant expression of BTEB2 was seen in neointimal SMCs. Atherectomy specimens obtained from primary and restenotic lesions showed predominant expression of BTEB2 to stellate SMCs. The incidence of restenosis in primary lesions was significantly higher in lesions containing BTEB2-positive cells than in lesions without (55.6% versus 25.0%, P=0.01).

Conclusions—The present study shows that BTEB2 expression is developmentally and pathologically regulated. BTEB2 is preferentially expressed in dedifferentiated or activated SMCs. Examination of human coronary artery specimens suggests that primary lesions containing BTEB2-positive cells are associated with higher risk of restenosis than BTEB2-negative lesions. These results suggest that BTEB2 can serve as a molecular marker for phenotypic modulation of vascular SMCs.

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

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