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http://purl.uniprot.org/citations/27440004http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27440004http://www.w3.org/2000/01/rdf-schema#comment"

Background

Inhibitors of cyclooxygenase-2 alleviate pain and reduce fever and inflammation by suppressing the biosynthesis of prostacyclin (PGI2) and prostaglandin E2. However, suppression of these prostaglandins, particularly PGI2, by cyclooxygenase-2 inhibition or deletion of its I prostanoid receptor also predisposes to accelerated atherogenesis and thrombosis in mice. By contrast, deletion of microsomal prostaglandin E synthase 1 (mPGES-1) confers analgesia, attenuates atherogenesis, and fails to accelerate thrombogenesis, while suppressing prostaglandin E2, but increasing biosynthesis of PGI2.

Methods

To address the cardioprotective contribution of PGI2, we generated mice lacking the I prostanoid receptor together with mPges-1 on a hyperlipidemic background (low-density lipoprotein receptor knockouts).

Results

mPges-1 depletion modestly increased thrombogenesis, but this response was markedly further augmented by coincident deletion of the I prostanoid receptor (n=10-18). By contrast, deletion of the I prostanoid receptor had no effect on the attenuation of atherogenesis by mPGES-1 deletion in the low-density lipoprotein receptor knockout mice (n=17-21).

Conclusions

Although suppression of prostaglandin E2 accounts for the protective effect of mPGES-1 deletion in atherosclerosis, augmentation of PGI2 is the dominant contributor to its favorable thrombogenic profile. The divergent effects on these prostaglandins suggest that inhibitors of mPGES-1 may be less likely to cause cardiovascular adverse effects than nonsteroidal anti-inflammatory drugs specific for inhibition of cyclooxygenase-2."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.116.022308"xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Chen L."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"FitzGerald G.A."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Tang S.Y."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Pawelzik S.C."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Lawson J."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Todd L."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Pure E."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"Monslow J."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/author"R Grant G."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/pages"328-338"xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/title"Cardiovascular Consequences of Prostanoid I Receptor Deletion in Microsomal Prostaglandin E Synthase-1-Deficient Hyperlipidemic Mice."xsd:string
http://purl.uniprot.org/citations/27440004http://purl.uniprot.org/core/volume"134"xsd:string
http://purl.uniprot.org/citations/27440004http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27440004
http://purl.uniprot.org/citations/27440004http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27440004
http://purl.uniprot.org/uniprot/#_A0A1L1SRE8-mappedCitation-27440004http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27440004
http://purl.uniprot.org/uniprot/#_E9PY53-mappedCitation-27440004http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27440004
http://purl.uniprot.org/uniprot/#_P35951-mappedCitation-27440004http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27440004
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http://purl.uniprot.org/uniprot/#_Q3U8R7-mappedCitation-27440004http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27440004
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