The effects of PPAR-γ ligand pioglitazone on platelet aggregation and arterial thrombus formation

• Published in: Cardiovascular research 2005-03, Vol.65 (4), p.907-912
• Main Authors: DAYUAN LI, KUI CHEN, SINHA, Nandita, XINGJIANG ZHANG, YIN WANG, SINHA, Anjan K, ROMEO, Francesco, MEHTA, Jawahar L
• Format: Article
• Language: English
• Subjects: Animals; Aorta - metabolism; Biological and medical sciences; Cardiology. Vascular system; Endothelium, Vascular - metabolism; Gene Expression Regulation - drug effects; Hypoglycemic Agents - therapeutic use; Ligands; Male; Medical sciences; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Platelet Aggregation - drug effects; PPAR gamma - agonists; PPAR gamma - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Thiazolidinediones - therapeutic use; Thrombomodulin - genetics; Thrombomodulin - metabolism; Thrombosis - blood; Thrombosis - pathology; Thrombosis - prevention & control
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2004.11.027

It has been suggested that peroxisome proliferator-activated receptor (PPAR)-gamma ligands reduce the development of atherosclerosis and myocardial ischemia-reperfusion injury; both of these phenomena are associated with platelet activation. We postulated that PPAR-gamma activation would inhibit platelet activation and intra-arterial thrombus formation. Sprague-Dawley rats were fed chow mixed with pioglitazone (1 or 10 mg/kg/day) for 7 to 10 days. A filter soaked in 30% FeCl(3) was applied around the abdominal aorta to study the patterns of arterial thrombogenesis. The aortic blood flow was continuously monitored using an ultrasonic Doppler flow probe. ADP and arachidonic acid-induced platelet aggregation and the expression of constitutive nitric oxide synthase (cNOS) and thrombomodulin in aorta were measured. Pioglitazone feeding delayed the time to occlusive thrombus formation by 40% (P