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

The dedifferentiation and the abnormal growth of vascular smooth muscle cel ls (VSMC) is a major component of vascular diseases. Hexamethylene-bis-acet amide (HMBA) has recently been shown to modulate the differentiation and gr owth of VSMC in vitro and in vivo. To determine the mechanism of this effec t, 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 extensio n and cDNA screening, we isolated a novel gene, HEXIM1, that is up-regulate d 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 an d was sustained for 48 h. These results suggest that HEXIM1 plays an import ant role in the regulation of the growth and differentiation of VSMC.