title: Level of adenosine diphosphate receptor P2Y12 blockade during percutaneous coronary intervention predicts the extent of endothelial injury, assessed by circulating endothelial cell measurement.
abstract: OBJECTIVE
  We aimed to investigate whether clopidogrel-induced inhibition of platelet reactivity could reduce the level of circulating endothelial cells (CEC), reflecting the endothelial injury induced by percutaneous coronary intervention (PCI).
  
  
  BACKGROUND
  Clopidogrel loading dose before percutaneous coronary angioplasty (PCI) reduces platelet activation through a selective and irreversible blockade of the adenosine diphosphate (ADP) receptor P2Y(12). The impact of clopidogrel on endothelial cells has been scarcely studied.
  
  
  METHODS
  A total of 149 patients undergoing PCI for stable angina were enrolled. Levels of CEC were measured at baseline (H0) and 6 (H6) and 24 (H24) h after the procedure using a CD146-based immunomagnetic separation assay. The CEC delta-change (CEC at H6 - CEC at H0) was analyzed according to ADP receptor P2Y(12) blockade, assessed by a vasodilator-stimulated phosphoprotein (VASP) assay after a 600-mg loading dose of clopidogrel.
  
  
  RESULTS
  The PCI induced a significant rise in CEC levels 6 h after the procedure. The CEC peak value was significantly higher in patients with high on-treatment platelet reactivity (VASP index ≥50%: 59.6 ± 27.5 cells/ml) as compared with good responders (VASP index <50%: 27 ± 22 cells/ml; p = 0.04). The endothelial injury, assessed by CEC delta-change between H6 and H0, was significantly higher in the high on-treatment platelet reactivity group compared with the good responders group (52.6 ± 25.6 vs. 18.6 ± 23.5, respectively; p < 0.001) and correlated with the VASP index (r = 0.59; p < 0.001). In multivariate analysis, VASP group, the number of diseased vessels, and the number of implanted stents independently predicted the endothelial injury (p < 0.001).
  
  
  CONCLUSIONS
  Optimal ADP receptor P2Y(12) blockade reduces the endothelial injury during PCI. This protective effect of clopidogrel on endothelial cells could add to the clinical benefit associated with this drug.
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord, Assistance Publique-Hôpitaux de Marseille, Université Aix-Méditerranée, Faculté de Médecine, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.forename: Karim
authors.initials: K
authors.lastname: Harhouri
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.forename: Karine
authors.initials: K
authors.lastname: Baumstarck-Barrau
authors.forename: Omar
authors.initials: O
authors.lastname: Ait-Mokhtar
authors.forename: François
authors.initials: F
authors.lastname: Roubille
authors.forename: Christophe
authors.initials: C
authors.lastname: Piot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lesavre
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
mesh_terms: D000787:Angina Pectoris / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011237:Predictive Value of Tests; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014652:Vascular Diseases / Q000175:diagnosis* / Q000209:etiology
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine