Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

OBJECTIVE: Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. MATERIALS AND METHODS: Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. RESULTS: Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. CONCLUSIONS: This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

SCH 79797, a selective PAR1 antagonist, protects against ischemia/reperfusion-induced arrhythmias in the rat hearts.

OBJECTIVE: Thrombin is implicated in the genesis of arrhythmias and activation of thrombin receptors exacerbated ventricular arrhythmias following coronary artery ligation. The present study was designed to investigate the possible protective effect of the protease-activated receptor-1 antagonist, SCH79797 against ischemia and reperfusion arrhythmias in the rat heart. MATERIALS AND METHODS: Healthy male Wistar rats (250-350 g) were anesthetized with urethane. Coronary artery ligation was performed for 5 minutes followed by 10 minutes reperfusion. Rhythm disturbances were monitored throughout the ischemia and reperfusion periods. Drugs injected were SCH79797 dihydrochloride (6.25, 12.5, 25 and 100 µg/kg), glibenclamide (5 mg/kg) and N-nitro L-arginine methyl-ester hydrochloride (25 mg/kg). The control group was injected with dimethylsulfoxide (0.1 ml). RESULTS: SCH79797 dihydrochloride reduced the number of premature contraction, prevalence and duration of ventricular tachycardia, prevalence and duration of ventricular fibrillation during both the ischemic and reperfusion periods in a dose-dependent manner. There is a trend for N-nitro L-arginine methyl-ester hydrochloride to increase all parameters of arrhythmias in SCH79797 dihydrochloride (25 µg/kg) treated rats, but glibenclamide (5 mg/kg) significantly (p < 0.05) increased these parameters. CONCLUSIONS: SCH79797 dihydrochloride induced an antiarrhythmic effect in the anesthetized rat. This protective effect could possibly be mediated by activation of nitric oxide synthase and/or of ATP-sensitive potassium channels.