RGD Reference Report - Determinants of thromboxane biosynthesis in rheumatoid arthritis: Role of RAGE and oxidant stress. - Rat Genome Database

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Determinants of thromboxane biosynthesis in rheumatoid arthritis: Role of RAGE and oxidant stress.

Authors: Ferrante, E  Vazzana, N  Santilli, F  Di Cicco, M  Lauriti, C  Di Battista, L  Ciabattoni, G  Di Matteo, L  Davi, G 
Citation: Ferrante E, etal., Free Radic Biol Med. 2010 Sep 1;49(5):857-64. doi: 10.1016/j.freeradbiomed.2010.06.009. Epub 2010 Jun 10.
RGD ID: 7244141
Pubmed: PMID:20541603   (View Abstract at PubMed)
DOI: DOI:10.1016/j.freeradbiomed.2010.06.009   (Journal Full-text)

Thromboxane (TX) biosynthesis by platelets and other cells in response to inflammatory triggers may provide a link between chronic inflammatory disease and atherothrombosis in rheumatoid arthritis (RA). In this study, we investigated the determinants of TX biosynthesis in RA, with particular reference to enhanced oxidative stress, receptor for advanced glycation end-products (RAGE) hyperactivity, and anti-tumor necrosis factor (TNF) treatment. Fifty-four patients with RA and 20 healthy subjects were recruited and a cross-sectional comparison of urinary 11-dehydro-TXB(2), 8-iso-PGF(2alpha), and plasma endogenous secretory RAGE (esRAGE) levels was performed between patients and controls. Urinary 11-dehydro-TXB(2) was significantly higher in RA patients than in healthy controls [425 (309-592) vs 233 (158-327) pg/mg creatinine, P<0.0001]. Furthermore, urinary 8-iso-PGF(2alpha) [323 (221-515) vs 172 (91-292) pg/mg creatinine, P<0.0001] and plasma esRAGE [155 (100-240) vs 377 (195-486) pg/ml, P=0.001] were higher and lower, respectively, in patients than in controls. A direct correlation was found between urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) only in patients not on anti-TNF therapy (r=0.420, P=0.021). Conversely, patients on anti-TNF therapy showed significantly lower urinary 8-iso-PGF(2alpha) [284 (201-373) vs 404 (241-539) pg/mg creatinine, P=0.043] but not 11-dehydro-TXB(2) than anti-TNF-treated subjects, with esRAGE as the only independent predictor of 11-dehydro-TXB(2) in this group of patients (adjusted R(2)=0.496, beta=-0.725, SEM=0.025, P=0.001). In conclusion, we provide biochemical evidence of enhanced TX biosynthesis in patients with RA, driven, at least in part, by lipid peroxidation. Treatment with anti-TNF agents may blunt isoprostane generation in the absence of significant effects on TX biosynthesis. We suggest that RAGE hyperactivity may escape TNF blockade, thus contributing to persistent TX biosynthesis in this setting.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
rheumatoid arthritis  IEP 7244141protein:decreased expression:plasma (human)RGD 
rheumatoid arthritis  ISOAGER (Homo sapiens)7244141; 7244141protein:decreased expression:plasma (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Mus musculus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Homo sapiens)
AGER  (advanced glycosylation end-product specific receptor)


Additional Information