title: ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression.
abstract: OBJECTIVE
  Angiotensin converting enzyme (ACE) inhibitors significantly improve survival in patients with atherosclerosis. Although ACE inhibitors reduce local angiotensin II (AngII) formation, serine proteases form AngII to an enormous amount independently from ACE. Therefore, our study concentrates on the effect of the ACE-inhibitor ramiprilat on chemokine release, AngII receptor (ATR) expression, and NF-kappaB activity in monocytes stimulated with AngII.
  
  
  RESULTS
  AngII-induced upregulation of IL-8 and MCP-1 protein and RNA in monocytes was inhibited by the AT1R-blocker losartan, but not by the AT2R-blocker PD 123.319. Ramiprilat dose-dependently suppressed AngII-induced upregulation of IL-8 and MCP-1. The suppressive effect of ramiprilat on AngII-induced chemokine production and release was in part caused by downregulation of NF-kappaB, but more by a selective and highly significant reduced expression of AT1 receptors as shown in monocytes and endothelial cells.
  
  
  CONCLUSIONS
  In our study we demonstrated for the first time that ramiprilat reduced expression of AT1R in monocytes and endothelial cells. In addition, ramiprilat downregulated NF-kappaB activity and thereby reduced the AngII-induced release of IL-8 and MCP-1 in monocytes. This antiinflammatory effect, at least in part, may contribute to the clinical benefit of the ACE inhibitor in the treatment of coronary artery disease.
authors.affiliation: Medical Clinic II, University of Technology, Dresden, Germany. AlexanderSchmeis@t-online.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmeisser
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Thomas
authors.initials: T
authors.lastname: Illmer
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.forename: Saeed
authors.initials: S
authors.lastname: Eskafi
authors.forename: Olaf
authors.initials: O
authors.lastname: Roerick
authors.forename: Christoph
authors.initials: C
authors.lastname: Gabler
authors.forename: Ruth
authors.initials: R
authors.lastname: Strasser
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019808:Losartan / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis; D019821:Simvastatin / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D007093:Imidazoles; D016209:Interleukin-8; D016328:NF-kappa B; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; C052549:ramiprilat; D019821:Simvastatin; D007703:Peptidyl-Dipeptidase A; D019808:Losartan; D017257:Ramipril