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Effect of clopidogrel on the expression of inflammatory markers in rabbit ischemic coronary artery
Laura Molero1, Antonio López-Farré, Petra J Mateos-Cáceres
1Cardiovascular Research Unit, Cardiology Department, Profesor Martín Lagos s/n, Hospital Clínico San Carlos, Cardiovascular Institute, Madrid, Spain.
Insights
Clopidogrel, an antiplatelet medication, demonstrated anti-inflammatory effects in a rabbit model of myocardial infarction. It reduced inflammatory markers like P-selectin and CD40 ligand in the ischemic coronary artery.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Inflammation Research
Background:
- Platelet activation and inflammation are key in acute coronary syndromes.
- Platelets can worsen ischemic injury by promoting inflammation in leukocytes and endothelial cells.
- Glycoprotein IIb/IIIa inhibitors reduce platelet aggregation and inflammation in acute coronary syndromes.
Purpose of the Study:
- To investigate if clopidogrel, an antiplatelet agent, exhibits anti-inflammatory effects during myocardial infarction.
- To assess clopidogrel's impact on inflammatory markers in the ischemic coronary artery.
Main Methods:
- Myocardial infarction was induced in rabbits by ligating the left anterior descending coronary artery.
- Rabbits received clopidogrel orally after arterial occlusion and reperfusion.
- Expression of P-selectin, CD40 ligand, tissue factor, and endothelial nitric oxide synthase was analyzed in the ischemic coronary artery.
Main Results:
- P-selectin expression significantly increased in infarcted rabbits compared to controls.
- Clopidogrel administration reduced P-selectin, CD40 ligand, and tissue factor expression.
- Clopidogrel preserved endothelial nitric oxide synthase protein expression in the ischemic coronary artery.
Conclusions:
- Inhibition of platelet activation by clopidogrel exerts significant anti-inflammatory effects.
- Clopidogrel may offer therapeutic benefits beyond platelet aggregation inhibition in myocardial infarction.
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.
