S Guillou1, S Tamareille2, S Giraud3, G Poitevin4, D Prunier-Mirebeau5, P Nguyen4, F Prunier6, L Macchi7. 1. CHU Poitiers, Service d'Hématologie Biologique, Poitiers, France; Université de Poitiers, INSERM U1082 IRTOMIT, Poitiers, France; Université d'Angers, EA3860 CRT, Angers, France. 2. Université d'Angers, EA3860 CRT, Angers, France; Institut MITOVASC, Angers, France. 3. Université de Poitiers, INSERM U1082 IRTOMIT, Poitiers, France. 4. Université de Reims, EA3801 HERVI, Reims, France. 5. Institut MITOVASC, Angers, France; CHU Angers, Département de biochimie et génétique, Angers, France; Université d'Angers, INSERM U1083, CNRS UMR 6214, Angers, France. 6. Université d'Angers, EA3860 CRT, Angers, France; Institut MITOVASC, Angers, France; CHU Angers, Service de Cardiologie, Angers, France. 7. CHU Poitiers, Service d'Hématologie Biologique, Poitiers, France; Université de Poitiers, INSERM U1082 IRTOMIT, Poitiers, France. Electronic address: laurent.macchi@chu-poitiers.fr.
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 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min 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 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion. Rats were randomized into four groups: control 30min (n=7), FDX 30min (n=7), control 2h (n=7), and FDX 2h (n=7). The FDX groups received 10mg/kg injection of FDX 10min 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 2h 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.
INTRODUCTION:Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min 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 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion. Rats were randomized into four groups: control 30min (n=7), FDX 30min (n=7), control 2h (n=7), and FDX2h (n=7). The FDX groups received 10mg/kg injection of FDX 10min 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 2h 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.
Authors: Gregory Stone; Ashley Choi; Oliva Meritxell; Joshua Gorham; Mahyar Heydarpour; Christine E Seidman; Jon G Seidman; Sary F Aranki; Simon C Body; Vincent J Carey; Benjamin A Raby; Barbara E Stranger; Jochen D Muehlschlegel Journal: Hum Mol Genet Date: 2019-05-15 Impact factor: 6.150
Authors: Ravi S Keshari; Robert Silasi; Narcis I Popescu; Constantin Georgescu; Hala Chaaban; Cristina Lupu; Owen J T McCarty; Charles T Esmon; Florea Lupu Journal: J Thromb Haemost Date: 2019-10-16 Impact factor: 5.824