Antiplatelet aggregation and endothelial protection of I4, a new synthetic anti-diabetes sulfonylurea compound. (June 2015)

• Record Type: Journal Article
• Authors: Ma, Lingman; Lu, Na; Wu, Guanzhong
• Is Part Of: Platelets. Volume 26:Number 4(2015:Jun.)
• Page Start: 342
• Page End: 348
• Publication Date: 2015-06
• Subjects: Blood platelets -- Periodicals; Blood Platelets -- Periodicals; 615.39
• DOI: 10.3109/09537104.2014.912749
• Languages: English
• ISSNs: 0953-7104

Abstract

<abstract> <title>Abstract</title> <p>I<sub>4</sub> is a new synthetic anti-diabetes sulfonylurea compound. The aim of present study was to investigate the preventive effects and primary action mechanisms of I<sub>4</sub> on platelet-mediated arterial thrombosis. Platelet aggregation and 5-hydroxytryptamine (5-HT) secretion <italic>ex vivo</italic> was detected. The time-to-occlusion (TTO), thrombus weight and content of von Willebrand factor (vWF) in rat model of electrical- and ferric chloride-induced vessel occlusion were determined. Meanwhile, a rat model of type 2 diabetes mellitus (T2DM) was established to evaluate the effect of I<sub>4</sub> on levels of plasma p-selectin, 6-keto-prostaglandin F<sub>1a</sub> (6-keto-PGF<sub>1a</sub>), thromboxane B<sub>2</sub> (TXB<sub>2</sub>), tissue-type plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1). NO synthesis, NOS activity, adhesion of platelet toward endothelial cell and intercellular adhesion molecule-1 (ICAM-1) expression were examined. Results showed that I<sub>4</sub> exhibited a higher inhibitory potency than Glimepiride on ADP-induced platelet aggregation and 5-HT release <italic>ex vivo</italic>. In addition, I<sub>4</sub> reduced the thrombus weight and content of vWF and markedly prolonged TTO. Oral administration of I<sub>4</sub> (1 ∼ 10 mg/kg) inhibited p-selectin production, elevated the ratio of plasma 6-keto-PGF<sub>1a</sub>/TXB<sub>2</sub> and t-PA/PAI-1 in T2DM rats. Furthermore, I<sub>4</sub> significantly improved NO synthesis and NOS activity, lowered adhesion ratio of platelet toward endothelial cells and ICAM-1 expression on HUVECs. These observations suggest that I<sub>4</sub> markedly improves platelet-mediated arterial thrombosis by inhibiting platelet activation and release reaction, ameliorating the endothelial dysfunction such as the suppression of vWF production and the reduction of the overexpression of ICAM-1, displayed its potential in alleviating diabetes-associated vascular complications.</p> </abstract>