title: Role of raloxifene on platelet metabolism and plasma lipids.
abstract: BACKGROUND
  This study was performed to understand the metabolic effects of raloxifene, a selective oestrogen receptor modulator, on platelets in healthy non-obese postmenopausal women. The data were compared to untreated subjects.
  
  
  METHODS
  Platelet nitric oxide activity (NO) and peroxynitrite level, platelet inducible and endothelial nitric oxide synthase expression and plasma lipids were evaluated at baseline and after 12 months of raloxifene or placebo treatment.
  
  
  RESULTS
  A significant increase of platelet NO and reduction of platelet peroxynitrite levels, as well as a decrease of inducible nitric oxide synthase expression, was observed 12 months after raloxifene therapy as compared to baseline or placebo treatment. Moreover, raloxifene treatment caused a significant increase in high-density lipoprotein cholesterol and a decrease of total cholesterol and low-density lipoprotein cholesterol were observed versus baseline values (P < 0.05). A significant positive correlation was observed between high-density lipoprotein cholesterol and platelet NO (r = 0.76, P < 0.005) in the raloxifene group.
  
  
  CONCLUSIONS
  Our results showed that raloxifene improves platelet metabolism in healthy postmenopausal women through an increase of the bioavailability of platelet NO by a reduction of iNOS and the beneficial effects on lipid metabolism. This mechanism of action of raloxifene on platelet activity may explain some cardiovascular protective effects of this selective oestrogen receptor modulator.
authors.affiliation: Istituto di Biochimica, Università Politecnica delle Marche, Ancona, Italy. l_nanetti@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Nanetti
authors.forename: A
authors.initials: A
authors.lastname: Camilletti
authors.forename: C M
authors.initials: CM
authors.lastname: Francucci
authors.forename: A
authors.initials: A
authors.lastname: Vignini
authors.forename: F
authors.initials: F
authors.lastname: Raffaelli
authors.forename: L
authors.initials: L
authors.lastname: Mazzanti
authors.forename: M
authors.initials: M
authors.lastname: Boscaro
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D010979:Platelet Function Tests; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012044:Regression Analysis
chemical_list: D004965:Estrogen Antagonists; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D019001:Nitric Oxide Synthase