title: Nuclear factor-kappaB as a hormonal intracellular signaling molecule: focus on angiotensin II-induced cardiovascular and renal injury.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Laboratory of Receptor and Signal Transduction, Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Hospital, and Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48202, USA.
authors: Xiao C
authors: XC
authors: Li
authors: Jia L
authors: JL
authors: Zhuo
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D000804:Angiotensin II