BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model.

Basic transcription element-binding protein 2 (BTEB2) is a regulator of the proliferation and phenotypic changes of vascular smooth muscle cells (SMCs). The aim of the present study was to determine whether or not BTEB2 knockdown inhibits balloon injury-induced neointimal hyperplasia attributed to the proliferation and phenotypic changes of vascular SMCs. We found that the knockdown of BTEB2 with antisense oligonucleotides (Ad-As-BTEB2) significantly reduced the intima/media ratio compared to uninjured arteries and vessels treated with Ad-LacZ. Knockdown of BTEB2 suppresses the proliferation of cultured vascular SMCs, concurrent with the down-regulation of proliferating cell nuclear antigen, angiotensin II type 1 receptor and platelet-derived growth factor BB. In addition, BTEB2 knockdown caused the up-regulation of the differentiation marker smooth muscle α-actin and down-regulation of the dedifferentiation marker embryonic smooth muscle myosin heavy chain. The present study provides direct evidence that BTEB2 plays a critical role in balloon injury-induced neointimal hyperplasia, which is closely linked to vascular SMC proliferation and phenotypic modulation. This study highlights the fact that BTEB2 may be a potential target for the prevention of restenosis after vascular intervention.