title: Effect of clopidogrel on the expression of inflammatory markers in rabbit ischemic coronary artery.
abstract: Inflammation and platelet activation are critical phenomena in the setting of acute coronary syndromes. Platelets may contribute to increase ischemic injury by enhancing the inflammatory response of leukocytes and endothelial myocardial cells. Pharmacological inhibition of platelet activation prevents ischemic complications in patients with coronary diseases. Agents directed against the integrin glycoprotein IIb/IIIa (GP IIb/IIIa) receptor not only inhibit platelet aggregation but also have been demonstrated to limit the inflammatory response in acute coronary syndromes. The question then raised is if the inhibition of platelet activation by other mechanisms than the blockade of GP IIb/IIIa may also exert anti-inflammatory effects. The aim of the present study was to analyze if clopidogrel may exert anti-inflammatory effects during the acute phase of myocardial infarction. A ligature was placed around the left anterior descending coronary artery of New Zealand White rabbits. After 15 min of ischemia, the myocardium was reperfused and the ischemic coronary artery was isolated 24 h after the ischemia. A group of ischemic rabbits was given a single oral dose of clopidogrel (20 mg kg(-1)) just after the arterial occlusion and the animal was recovered. Sham-operated animals served as control. P-selectin expression was significantly increased in infarcted rabbits with respect to control rabbits. Clopidogrel administration reduced P-selectin expression with respect to untreated infarcted rabbits. CD40 ligand and tissue factor expression was increased in the ischemic coronary artery and reduced after clopidogrel administration. Clopidogrel also protected endothelial nitric oxide synthase protein expression in the ischemic coronary artery, a protein that has been found downregulated under inflammatory conditions. In conclusion, inhibition of platelet activation by clopidogrel exerted anti-inflammatory effects on the ischemic coronary artery.
authors.affiliation: Cardiovascular Research Unit, Cardiology Department, Profesor Martín Lagos s/n, Hospital Clínico San Carlos, Cardiovascular Institute, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Molero
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Farré
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Mateos-Cáceres
authors.forename: Ruth
authors.initials: R
authors.lastname: Fernández-Sánchez
authors.forename: María
authors.initials: M
authors.lastname: Luisa Maestro
authors.forename: Jacobo
authors.initials: J
authors.lastname: Silva
authors.forename: Enrique
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D023201:CD40 Ligand / Q000378:metabolism; D000077144:Clopidogrel; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D019007:P-Selectin / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011817:Rabbits; D013925:Thromboplastin / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D013925:Thromboplastin; D000077144:Clopidogrel; D013988:Ticlopidine