Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction. Issue 141 (May 2016)

• Record Type: Journal Article
• Authors: Guillou, S.; Tamareille, S.; Giraud, S.; Poitevin, G.; Prunier-Mirebeau, D.; Nguyen, P.; Prunier, F.; Macchi, L.
• Is Part Of: Thrombosis research. Issue 141(2016)
• Page Start: 98
• Page End: 103
• Publication Date: 2016-05
• Subjects: Fondaparinux -- Vessels -- Inflammation -- Ischemia/reperfusion injury -- Thrombomodulin -- Endothelial protein C receptor; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.02.009
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2 h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30 min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels. Methods: Wistar male rats were subjected to 40 minutes (min) of myocardial ischemia, followed by 30 min or 2 h of reperfusion. Rats were randomized into four groups: control 30 min (n = 7), FDX 30 min (n = 7), control 2 h (n = 7), and FDX 2 h (n = 7). The FDX groups received 10 mg/kg injection of FDX 10 min prior to initiating reperfusion. We studied: 1) mRNA expression of endothelial markers, such as thrombomodulin (TM), endothelial protein C receptor (EPCR), and tissue factor (TF) and 2) proteic expression of ICAM-1, NF-κB, IκB, and JNK. Leukocyte infiltration was assessed by histochemistry. We also evaluated TM and EPCR mRNA expression in a model of isolated rat mesenteric arteries incubated with FDX. Results: FDX upregulated the expression of TM and EPCR mRNA in the models of myocardial infarction and isolated mesenteric arteries. No difference was observed between the treated and control groups regarding the expression of pro-inflammatory signaling proteins, adhesion molecules, and leukocyte infiltration after 2 h of reperfusion. Conclusion: The cardioprotective effect of FDX at early-stage reperfusion could be related to vascular protection, yet not to an anti-inflammatory effect. Highlights: Mechanisms involved in early fondaparinux-induced cardioprotection are proposed. No anti-inflammatory mechanism is related to this early protective effect. Fondaparinux upregulates the expression of protective endothelial markers. Fondaparinux cardioprotective effect appears to be related to vascular protection.