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

Background-We have previously shown BTEB2, a Kruppel-like zinc finger trans cription factor, to regulate expression of the SMemb/NMHC-B gene, which has been implicated in phenotypic modulation of smooth muscle cells (SMCs). Th e present study was done to assess the developmental and pathological expre ssion profiles of BTEB2 and to further evaluate the clinical relevance of B TEB2 expression in human coronary artery disease; Methods and Results-Immunohistochemistry showed developmentally regulated e xpression of BTEB2 with abundant expression in fetal but not in adult aorti c SMCs of humans and rabbits. In balloon-injured aortas, predominant expres sion of BTEB2 was seen in neointimal SMCs, Atherectomy specimens obtained f rom primary and restenotic lesions showed predominant expression of BTEB2 t o stellate SMCs. The incidence of restenosis in primary lesions was signifi cantly higher in lesions containing BTEB2-positive cells than in lesions wi thout (55.6% versus 25.0%, P=0.01). Conclusions-The present study shows that BTEB2 expression is developmentall y and pathologically regulated. BTEB2 is preferentially expressed in dediff erentiated or activated SMCs. Examination of human coronary artery specimen s suggests that primary lesions containing BTEB2-positive cells are associa ted with higher risk of restenosis than BTEB2-negative lesions. These resul ts suggest that BTEB2 can serve as a molecular marker for phenotypic modula tion of vascular SMCs.