Nuclear factor-kappaB as a hormonal intracellular signaling molecule: focus on angiotensin II-induced cardiovascular and renal injury.

PURPOSE OF REVIEW: Nuclear factor-kappaB (NF-kappaB) has recently emerged as a novel intracellular signaling molecule for hormones, cytokines, chemokines, and growth factors. The purpose of this article is to highlight the role of NF-kappaB as an intracellular signaling for angiotensin II and clinical perspectives of targeting NF-kappaB signaling in treating hypertensive and renal diseases. RECENT
FINDINGS: A selective review of recently published work provides strong evidence that activation of NF-kappaB signaling by angiotensin II mediates the detrimental effects of angiotensin II on the transcription of cytokines, chemokines and growth factors. Angiotensin II stimulates AT1 receptors to activate NF-kappaB signaling via both canonical (classical) and noncanonical (alternative) pathways. Intracellular angiotensin II may also induce NF-kappaB activation and transactivation of target genes. Nearly 800 NF-kappaB inhibitors have been described, but none has advanced to clinical trials. However, angiotensin converting enzyme inhibitors and AT1 blockers are beneficial in treating angiotensin II-induced hypertensive and renal injury in part by inhibiting NF-kappaB activation.
SUMMARY: Angiotensin II induces the transcription of cytokines, chemokines and growth factors, leading to target organ injury. These responses to angiotensin II are caused primarily by AT1 receptor-activated NF-kappaB signaling. Targeting NF-kappaB signaling with angiotensin converting enzyme inhibitors, AT1 blockers, and specific NF-kappaB inhibitors may represent a novel approach in treating angiotensin II-induced hypertensive and renal diseases.