title: Prolonged statin-associated reduction in neutrophil reactive oxygen species and angiotensin II type 1 receptor expression: 1-year follow-up.
abstract: OBJECTIVE
  Our study investigated reactive oxygen species (ROS) generation and angiotensin II type 1 receptor (AT(1)-R) expression in primed polymorphonuclear leukocytes (PMNs) of dyslipidaemic subjects over prolonged statin treatment.
  
  
  RESULTS
  Sixteen untreated dyslipidaemic subjects with moderately increased cardiovascular risk (National Cholesterol Education Program, Adult Treatment Panel III) were studied before and during long-term (1 year) simvastatin treatment. Neutrophils from dyslipidaemic subjects generated more ROS in comparison with cells from healthy control subjects. After 1 year of simvastatin treatment, ROS production (delta N-formyl-Met-Leu-Phe-induced generation and area under the curve) was significantly reduced. At baseline, AT1-R mRNA expression was also higher in dyslipidaemic subjects than in healthy controls and it was reduced after clinical treatment with simvastatin. In a subgroup of patients, a reduced angiotensin II-induced ROS generation was also observed upon clinical simvastatin treatment. Moreover, a direct effect of statin on the upregulated AT(1)-R expression was demonstrated in vitro in neutrophils of untreated dyslipidaemic subjects.
  
  
  CONCLUSIONS
  A consistent reversion of pro-inflammatory oxidative functional response and reduction of AT(1)-R expression in primed PMNs was observed in patients during long-term statin treatment. The AT1-R reduction over treatment may contribute to the normalization of dysregulated neutrophil activation which occurs in the pre-clinical phase of atherosclerosis.
authors.affiliation: Department of Clinical Medicine, University of Insubria, Viale Borri 57, Varese 21100, Italy. luigina.guasti@uninsubria.it
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.forename: Ramona C
authors.initials: RC
authors.lastname: Maio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rasini
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrari
authors.forename: Luana
authors.initials: L
authors.lastname: Castiglioni
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudio
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grandi
authors.forename: Sergio
authors.initials: S
authors.lastname: Lecchini
authors.forename: Achille
authors.initials: A
authors.lastname: Venco
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000188:drug therapy*; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D019821:Simvastatin / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D019821:Simvastatin