PROMOTER ANALYSIS OF HUMAN INDUCIBLE NITRIC-OXIDE SYNTHASE GENE ASSOCIATED WITH CARDIOVASCULAR HOMEOSTASIS

We previously showed that interferon (IFN)-gamma inhibited the prolife ration of rat vascular smooth muscle cells (VSMC) by generation of nit ric oxide (NO) through the induction of an NO synthase (NOS) and clone d the rat inducible NOS cDNA in VSMC (VSM-NOS). To study the regulatio n of human inducible NOS (hiNOS) transcription in VSMC, we now cloned and sequenced a 2.9-kb fragment for the hiNOS gene containing a putati ve promoter, exon 1 and exon 2. The 5'-flanking region contains severa l consensus sequences for the binding of transcription factors involve d in the inducibility of other genes by cytokines. These include IFN-g amma responsive element and NF-IL6 and NF-kappa B binding consensus se quences. Interestingly, hiNOS gene contains a shear-stress responsive element (GAGACC) which was also found to exist in human endothelial-ty pe NOS but not in murine inducible NOS. (C) 1994 Academic Press, Inc.