title: Simvastatin treatment in subjects at high cardiovascular risk modulates AT1R expression on circulating monocytes and T lymphocytes.
abstract: OBJECTIVE
  Angiotensin II, through the activation of angiotensin II type 1 receptors, plays a crucial role in atherosclerosis. Statins may interfere with the effects of angiotensin II.
  
  
  METHODS
  We have investigated the expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor and angiotensinogen on circulating monocytes and T-lymphocytes from subjects at high risk for vascular events before and during simvastatin treatment, and healthy controls. In-vitro experiments were also performed to assess the ability of simvastatin to interfere with angiotensin II signalling.
  
  
  RESULTS
  In comparison with controls, high-risk subjects had similar angiotensin II type 1 receptor expression on the cell membranes but significantly higher angiotensin II type 1 receptor mRNA levels at least in monocyte subsets whereas their expression on T cells was similar. Angiotensin II type 2 receptor mRNA expression was higher than controls in both monocytes and T lymphocytes. No differences were observed in angiotensinogen expression on monocytes while T lymphocytes of high-risk subjects show higher expression. One-month treatment of high-risk subjects with simvastatin resulted in a reduction of angiotensin II type 1 receptor mRNA without affecting angiotensin II type 2 receptor whereas angiotensinogen mRNA expression was reduced at least in monocytes. Incubation in vitro with simvastatin reduces the expression of angiotensin II type 1 receptor mRNA levels on monocytes from untreated subjects.
  
  
  CONCLUSIONS
  Simvastatin induces down-regulation of the angiotensin II type 1 receptor, interferes with angiotensin II activity in immune cells and contributes to the anti-inflammatory profile of statins that can explain the therapeutic effects of these drugs.
authors.affiliation: Section of Experimental and Clinical Pharmacology, Department of Clinical Medicine, University of Insubria, Varese, Italy. franca.marino@uninsubria.it
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rasini
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrari
authors.forename: Ramona Consuelo
authors.initials: RC
authors.lastname: Maio
authors.forename: Anna
authors.initials: A
authors.lastname: Loraschi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cimpanelli
authors.forename: Laura
authors.initials: L
authors.lastname: Schembri
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Legnaro
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Molteni
authors.forename: Chiara
authors.initials: C
authors.lastname: Crespi
authors.forename: Francesca
authors.initials: F
authors.lastname: Crema
authors.forename: Achille
authors.initials: A
authors.lastname: Venco
authors.forename: Sergio
authors.initials: S
authors.lastname: Lecchini
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; D019821:Simvastatin