title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Second Department of Internal Medicine, Gunma University School of Medicine, Gunma.
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshino
authors.forename: M
authors.initials: M
authors.lastname: Kurabayashi
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Sakamoto
authors.forename: E
authors.initials: E
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Kowase
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: I
authors.initials: I
authors.lastname: Manabe
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Takase
authors.forename: J N
authors.initials: JN
authors.lastname: Wilcox
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000328:Adult; D000800:Angioplasty, Balloon; D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D017225:Atherectomy, Coronary; D015415:Biomarkers; D002454:Cell Differentiation; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006083:Graft Occlusion, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011817:Rabbits; D012307:Risk Factors; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D015534:Trans-Activators