Angiotensin II induces gene transcription through cell-type-dependent effects on the nuclear factor-kappa B (NF-kappa B) transcription factor

The vasopressor octapeptide, angiotensin II (Ang II), exerts homeostatic re sponses in cardiovascular tissues, including the heart, blood vessel wall, adrenal cortex and liver (a major source of circulating plasma proteins). O ne of the effects of Ang II is to induce expression of regulatory, structur al and cytokine genes that play important roles in long-term control of blo od pressure, vascular remodeling, cardiac hypertrophy and inflammation. The identification of nuclear signaling pathways and target transcription fact ors has provide important insight into cellular responses and the spectrum of genes controlled by Ang II. Here we will review how Ang II activates the transcription factors, Activator Protein 1 (AP-1), Signal Transducer and A ctivator of Transcription (STATs), and Nuclear Factor-kappaB (NF-kappaB). N F-kappaB is of particular interest because it is an important mediator of r esynthesis of the Ang II precursor, angiotensinogen AGT. Through this posit ive feedback loop, long-term changes in the activity of the renin angiotens in system occur. Although NF-kappaB is ubiquitously expressed, surprisingly the mechanism for Ang II-inducible NF-kappaB regulation differs between ao rtic smooth muscle cells (VSMCs) and hepatocytes. In VSMC, Ang II induces n uclear translocation of cytoplasmic transactivatory NF-kappaB proteins thro ugh proteolysis of its inhibitor, I kappaB. By contrast, in hepatocytes, An g II induces large nuclear isoforms of NF-kB1 to bind DNA through a mechani sm independent of changes in I kappaB turnover. NF-kappaB activation depend s upon the activity of DAG-sensitive PKC isoforms and ROS signaling pathway . These observations indicate that significant differences exist in Ang II signaling depending upon cell-type involved and suggest the possibility tha t tissue-selective modulation of Ang II effects is possible in the cardiova scular system.