RGD Reference Report - Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction.

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Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction.
Authors:	Guillou, S Tamareille, S Giraud, S Poitevin, G Prunier-Mirebeau, D Nguyen, P Prunier, F Macchi, L
Citation:	Guillou S, etal., Thromb Res. 2016 May;141:98-103. doi: 10.1016/j.thromres.2016.02.009. Epub 2016 Feb 18.
RGD ID:	13515126
Pubmed:	PMID:26994471 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.thromres.2016.02.009 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PROCR	Human	Myocardial Reperfusion Injury	treatment	ISO	Procr (Rattus norvegicus)		RGD
Procr	Rat	Myocardial Reperfusion Injury	treatment	IDA			RGD
Procr	Mouse	Myocardial Reperfusion Injury	treatment	ISO	Procr (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Procr (protein C receptor)

Genes (Mus musculus)

Procr (protein C receptor, endothelial)

Genes (Homo sapiens)

PROCR (protein C receptor)

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Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction.