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Factor Xa and factor IIa inhibitors differentially regulate inflammation in myocardial ischemia reperfusion injury [20-0174 RNA-seq]

ABSTRACT: While thrombin is the key protease in regard to thrombus formation, other coagulation proteases, such as fXa or activated protein C (aPC), independently modulate intracellular signaling via partially disjunct receptors. Hence, we postulate that inhibition of fXa or fIIa conveys different effects in myocardial ischemia-reperfusion injury (IRI) in regard to inflammation despite comparable anticoagulant efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE161324 | GEO | 2021/07/28

REPOSITORIES: GEO

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Factor Xa and factor IIa inhibitors differentially regulate inflammation in myocardial ischemia reperfusion injury [19-0267 RNA-seq]

Project description:While thrombin is the key protease in regard to thrombus formation, other coagulation proteases, such as fXa or activated protein C (aPC), independently modulate intracellular signaling via partially disjunct receptors. Hence, we postulate that inhibition of fXa or fIIa conveys different effects in myocardial ischemia-reperfusion injury (IRI) in regard to inflammation despite comparable anticoagulant efficacy.

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Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors.

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Factor Xa and factor IIa inhibitors differentially regulate inflammation in myocardial ischemia reperfusion injury

Project description:This SuperSeries is composed of the SubSeries listed below.

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Chemoenzymatic synthesis of heparin oligosaccharides with both anti-factor Xa and anti-factor IIa activities.

Project description:Heparan sulfate (HS) and heparin are highly sulfated polysaccharides. Heparin is a commonly used anticoagulant drug that inhibits the activities of factors Xa and IIa (also known as thrombin) to prevent blood clot formation. Here, we report the synthesis of a series of size-defined oligosaccharides to probe the minimum size requirement for an oligosaccharide with anti-IIa activity. The synthesis was completed by a chemoenzymatic approach involving glycosyltransferases, HS sulfotransferases, and C(5)-epimerase. We demonstrate the ability to synthesize highly purified N-sulfo-oligosaccharides having up to 21 saccharide residues. The results from anti-Xa and anti-IIa activity measurements revealed that an oligosaccharide longer than 19 saccharide residues is necessary to display anti-IIa activity. The oligosaccharides also exhibit low binding toward platelet factor 4, raising the possibility of preparing a synthetic heparin with a reduced effect of heparin-induced thrombocytopenia. The results from this study demonstrate the ability to synthesize large HS oligosaccharides and provide a unique tool to probe the structure and function relationships of HS that require the use of large HS fragments.

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Self-anticoagulant sponges for whole blood auto-transfusion and its mechanism of coagulation factor inactivation

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Coagulation Factor Xa

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Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis with no increased bleeding risk

2016-04-01 | GSE66724 | GEO