Upregulated Expression of Toll-like Receptor 4 in Peripheral Blood of Ischaemic Stroke Patients Correlates with Cyclooxygenase 2 Expression

• Published in: European journal of vascular and endovascular surgery 2011-03, Vol.41 (3), p.358-363
• Main Authors: Ferronato, S, Lira, M.G, Olivato, S, Scuro, A, Veraldi, G.F, Romanelli, M.G, Patuzzo, C, Malerba, G, Pignatti, P.F, Mazzucco, S
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Brain Ischemia - enzymology; Brain Ischemia - genetics; Brain Ischemia - immunology; Carotid Stenosis - enzymology; Carotid Stenosis - genetics; Carotid Stenosis - immunology; Carotid Stenosis - surgery; COX-2; Cyclooxygenase 2 - genetics; Endarterectomy, Carotid; Female; Gene expression; Humans; Intramolecular Oxidoreductases - genetics; Ischaemic stroke; Ischemic Attack, Transient - enzymology; Ischemic Attack, Transient - genetics; Ischemic Attack, Transient - immunology; Italy; Male; Middle Aged; Peripheral blood; Prostaglandin-E Synthases; Receptors, Prostaglandin E, EP3 Subtype - genetics; Receptors, Prostaglandin E, EP4 Subtype - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA - blood; Stroke - enzymology; Stroke - genetics; Stroke - immunology; Surgery; TLR4; Toll-Like Receptor 4 - genetics; Up-Regulation
• ISSN: 1078-5884; 1532-2165
• DOI: 10.1016/j.ejvs.2010.11.019

Abstract Objectives An inflammatory process following stroke in human brains and systemic inflammatory responses after stroke in humans have been reported by numerous investigators. The aim of the study was to investigate if genes involved in the cyclooxygenase 2 (COX-2) pathway are upregulated at peripheral level in patients after transient ischaemic attack (TIA) and stroke. Design of Study Blood samples were obtained from two groups of patients undergoing carotid endarterectomy. The first group included 25 patients who presented TIA or ischaemic stroke. The second group included 35 patients who had an asymptomatic internal carotid artery stenosis. Total RNA was isolated and the expression of Toll-like Receptor 4 (TLR4), COX-2, membrane-associated Prostaglandin E synthase (mPGES-1), Prostaglandin E2 receptors (EP3 and EP4) was analysed by real time RT-PCR. Results Expression of COX-2 and TLR4 were significantly increased in symptomatic patients ( p < 0.001). Correlation analysis showed that TLR4 expression significantly correlated with COX-2 expression ( R = 0.65; p < 0.01) in ischaemic stroke patients. This correlation was not observed in TIA and asymptomatic patients. Conclusions Our results suggest that the peripheral mechanism of inflammatory injury after stroke may be mediated by TLR4 through a COX-2-dependent pathway.