title: Ascorbic acid infusion blunts CD40L upregulation in patients undergoing coronary stent.
abstract: OBJECTIVE
  To reduce the increase of oxidative stress and the upregulation of CD40L during stenting procedure using ascorbic acid infusion.
  
  
  BACKGROUND
  CD40L upregulation occurring after coronary percutaneous coronary intervention predicts vascular events but the underlying mechanism is still unclear.
  
  
  METHODS
  Fifty-six patients undergoing elective coronary stenting were randomly allocated to intravenous infusion of the antioxidant ascorbic acid or placebo. Platelet CD40L and plasma levels of soluble CD40L and of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, were measured before and after coronary stenting. In vitro study was also done to measure reactive oxidant species and CD40L expression in platelets exposed to anoxia-reoxygenation.
  
  
  RESULTS
  Placebo-treated patients showed a significant increase of platelet CD40L, soluble CD40L and 8-hydroxy-2'-deoxyguanosine compared to baseline values. Patients given ascorbic acid showed no change of soluble CD40L and platelet CD40L but a significant decrease of 8-hydroxy-2'-deoxyguanosine. After 60 and 120 min, soluble CD40L, platelet CD40L and 8-hydroxy-2'-deoxyguanosine were significantly lower in the ascorbic acid-treated group compared to the placebo-treated one. A significant correlation between platelet CD40L and soluble CD40L and between soluble CD40L and 8-hydroxy-2'-deoxyguanosine was observed. Platelets, in vitro exposed to anoxia-reoxygenation, had a burst of ROS and an upregulation of CD40L that were inhibited by ascorbic acid or apocynin, an inhibitor of NADPH oxidase.
  
  
  CONCLUSIONS
  This study shows that in patients undergoing coronary stenting CD40L is upregulated with a mechanism which is likely mediated by oxidative stress.
authors.affiliation: Prima Clinica Medica-Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tanzilli
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Serena
authors.initials: S
authors.lastname: Di Santo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
authors.forename: Andrea
authors.initials: A
authors.lastname: Celestini
authors.forename: Marco
authors.initials: M
authors.lastname: Proietti
authors.forename: Priscilla
authors.initials: P
authors.lastname: Tovaglia
authors.forename: Enrico
authors.initials: E
authors.lastname: Mangieri
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000098:Acetophenones / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007262:Infusions, Intravenous; D007558:Italy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D010919:Placebos; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D015607:Stents; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D015415:Biomarkers; D004791:Enzyme Inhibitors; D010919:Placebos; D017382:Reactive Oxygen Species; D023201:CD40 Ligand; D000080242:8-Hydroxy-2'-Deoxyguanosine; C056165:acetovanillone; D019255:NADPH Oxidases; D003849:Deoxyguanosine; D001205:Ascorbic Acid