title: Inhibition of platelet function with clopidogrel is associated with a reduction of inflammation in patients with peripheral artery disease.
abstract: BACKGROUND
  The reactivity of platelets is increased in patients with peripheral artery disease (PAD). RANTES and sCD40L are chemokines which are stored in the alpha-granules of platelets. Clopidogrel inhibits and thus reduces platelet reactivity. Whether a treatment with clopidogrel is associated with an inhibition of systemic inflammation in patients with PAD has not been thoroughly explored. This study examined the effect of clopidogrel on platelet reactivation and the release of inflammatory chemokines in patients with PAD.
  
  
  METHODS
  40 patients with PAD were randomized into two groups. In the first group A the patients were treated with 100mg acetylsalicylic acid (ASA) and additional placebo for 4weeks. The patients in group B received 75mg/d clopidogrel in addition to ASA 100mg for 4weeks. After obtaining blood at days 0, 7 and 28 the platelet activation was determined by measuring the surface protein expression of CD63, CD62p and thrombospondin (TSP) after stimulation with TRAP and ADP. The release of the chemokines RANTES and sCD40L from platelets was analyzed by ELISA.
  
  
  RESULTS
  Platelet activation markers (CD62p and CD63) and chemokine RANTES were significantly reduced in patients with PAD after 7 and 28days after treatment with clopidogrel. No alterations were found in TSP expression and sCD40L during the treatment.
  
  
  CONCLUSIONS
  The treatment with clopidogrel leads to a reduction of platelet reactivity and release of RANTES from the platelets of patients with PAD.
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Weithaeuser
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Steffens
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bobbert
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Adel
authors.initials: A
authors.lastname: Hassanein
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Ayral
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Electronic address: ursula.rauch@charite.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005858:Germany; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood; D019007:P-Selectin / Q000097:blood; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D060149:Tetraspanin 30 / Q000097:blood; D019699:Thrombospondins / Q000097:blood; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C483024:CCL5 protein, human; C554586:CD63 protein, human; D018946:Chemokine CCL5; D018836:Inflammation Mediators; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; C546937:SELP protein, human; D060149:Tetraspanin 30; D019699:Thrombospondins; D023201:CD40 Ligand; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Inflammation; Peripheral artery disease; Platelets