Cloning of hexamethylene-bis-acetamide-inducible transcript, HEXIM1, in human vascular smooth muscle cells

The dedifferentiation and the abnormal growth of vascular smooth muscle cells (VSMC) is a major component of vascular diseases. Hexamethylene-bis-acetamide (HMBA) has recently been shown to modulate the differentiation and growth of VSMC in vitro and in vivo. To determine the mechanism of this effect, we treated human coronary artery VSMC with HMBA and analyzed the effect of HMBA on gene expression by mRNA differential display. HMBA modulated the expression of a number of specific message fragments. By Marathon extension and cDNA screening, we isolated a novel gene, HEXIM1, that is up-regulated in HMBA-stimulated VSMC. HEXIM1 cDNA has a length of 3624 bp and encodes for a protein of 359 amino acids. Northern blot analysis demonstrated that the level of HEXIM1 mRNA rapidly increased at 1 h after HMBA stimulation and was sustained for 48 h. These results suggest that HEXIM1 plays an important role in the regulation of the growth and differentiation of VSMC.