Effect of clopidogrel on the inflammatory progression of early atherosclerosis in rabbits model

• Published in: Atherosclerosis Vol. 194; no. 2; pp. 348 - 356
• Main Authors: Li, Ming, Zhang, Yijing, Ren, Hongsheng, Zhang, Yuanchao, Zhu, Xinglei
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.10.2007; Elsevier
• Subjects: Adhesion molecule; Animals; Aspirin - pharmacology; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - drug therapy; Atherosclerosis - pathology; Atorvastatin Calcium; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular system; Chemokine CCL2 - drug effects; Clopidogrel; Diet, Atherogenic; Disease Models, Animal; Femoral Artery - drug effects; Femoral Artery - pathology; Heptanoic Acids - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Inflammation - drug therapy; Intercellular Adhesion Molecule-1 - drug effects; Male; Medical sciences; Monocyte chemotactic protein-1; Neurology; P-selectin; P-Selectin - drug effects; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - pharmacology; Pyrroles - pharmacology; Rabbits; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Vascular Cell Adhesion Molecule-1 - drug effects; Vascular diseases and vascular malformations of the nervous system; Vasodilator agents. Cerebral vasodilators; Clopidogrel; Adhesion molecule; P-selectin; Atherosclerosis; Monocyte chemotactic protein-1; Prostaglandin-endoperoxide synthase; Rabbit; Lipids; Cardiovascular disease; Acetylsalicylic acid; Hypocholesterolemic agent; Vascular disease; HMG-CoA reductase inhibitor; Salicylates; Vascular wall; Monocyte; Intercellular adhesion molecule 1; Enzyme; Enzyme inhibitor; Statin derivative; Lagomorpha; Iliac artery; Cholesterol; Antiplatelet agent; Non steroidal antiinflammatory agent; P Selectin; Vertebrata; Mammalia; Analgesic; Treatment; Animal; Antipyretic; Atorvastatin; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Thienopyridine derivative; Caucasoid; Antilipemic agent
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2006.11.006

Abstract Atherosclerosis is an inflammatory response of the arterial wall to ‘injury’, which is prominently driven by inflammatory factors. Clopidogrel reduces early atherosclerosis, however, the role of clopidogrel in modulating inflammatory progression of atherosclerosis is less investigated. We wished to determine the effect of clopidogrel on progression of established atherosclerosis, vascular inflammatory factors and compared with that of aspirin and atorvastatin. Fifty male New Zealand white (NZW) rabbits were divided into five groups randomly including negative group. The rabbits were fed with a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except negative group were balloon injured 1 week after initiation of the diet, then animals were treated with clopidogrel (4 mg/kg/day), aspirin (12 mg/kg/day), atorvastatin (2.5 mg/kg/day) or placebo for 6 weeks. At the end of the study, the placebo (positive) group had significant progression of atherosclerosis compared with negative group. In contrast, clopidogrel, aspirin or atorvastatin treated rabbits showed a significant reduction in progression of atherosclerosis and decreased the levels of P-selection, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in serum and vascular wall. Among three drugs, the action of clopidogrel is the most powerful in decreasing the levels of inflammatory factors. These results suggest that in a rabbit atherosclerosis model, clopidogrel retards the progression of established lesions and that this effect is paralleled by a suppression of inflammatory factors.