Biros, E, Moran, CS, Maguire, J, Holliday, E, Levi, C & Golledge, J 2017, 'Upregulation of arylsulfatase B in carotid atherosclerosis is associated with symptoms of cerebral embolization.', Scientific Reports, vol. 7, no. 1, pp. 4338-4338.View/Download from: UTS OPUS or Publisher's site
The aim of this study was to identify genes for which the expression within carotid atherosclerosis was reproducibly associated with the symptoms of cerebral embolization. Two publically available microarray datasets E-MEXP-2257 and GSE21545 were analysed using GeneSpring 11.5. The two datasets utilized a total of 22 and 126 carotid atherosclerosis samples, obtained from patients with and without symptoms of cerebral embolization, respectively. To assess whether the findings were reproducible we analysed carotid atherosclerosis samples from another 8 patients with and 7 patients without symptoms of cerebral embolization using real-time PCR. In vitro studies using VSMC were performed to assess the functional relevance of one of the validated genes. We identified 1624 and 135 differentially expressed genes within carotid atherosclerosis samples of symptomatic compared to asymptomatic patients using the E-MEXP-2257 and GSE21545 datasets, respectively (≥1.15-absolute fold-change, P < 0.05). Only 7 differentially expressed genes or 0.4% (7/1,752) were consistent between the datasets. We validated the differential expression of ARSB which was upregulated 1.15-fold (P = 0.029) in atherosclerosis from symptomatic patients. In vitro incubation of VSMCs with the ARSB inhibitor L-ascorbic acid resulted in marked upregulation of SIRT1 and AMPK. This study suggests that ARSB may represent a novel target to limit carotid embolization.
Majersik, JJ, Cole, JW, Golledge, J, Rost, NS, Chan, Y-FY, Gurol, ME, Lindgren, AG, Woo, D, Fernandez-Cadenas, I, Chen, DT, Thijs, V, Worrall, BB, Kamal, A, Bentley, P, Wardlaw, JM, Ruigrok, YM, Battey, TWK, Schmidt, R, Montaner, J, Giese, A-K, Roquer, J, Jimenez-Conde, J, Lee, C, Ay, H, Jose Martin, J, Rosand, J & Maguire, J 2015, 'Recommendations From the International Stroke Genetics Consortium, Part 1 Standardized Phenotypic Data Collection', STROKE, vol. 46, no. 1, pp. 279-+.View/Download from: UTS OPUS or Publisher's site
Moxon, JV, Liu, D, Moran, CS, Crossman, DJ, Krishna, SM, Yonglitthipagon, P, Emeto, TI, Morris, DR, Padula, M, Mulvenna, JP, Rush, CM & Golledge, J 2014, 'Proteomic and genomic analyses suggest the association of Apolipoprotein C1 with abdominal aortic aneurysm.', PROTEOMICS - Clinical Applications, vol. 8, no. 9-10, pp. 762-772.View/Download from: UTS OPUS or Publisher's site
Abdominal aortic aneurysm (AAA) is an important cause of mortality in the elderly. Mouse models are widely used to investigate AAA pathogenesis but their suitability for biomarker discovery is unexplored.
We conducted a three-phase study. Phase 1: Aortas from angiotensin-II-infused apolipoprotein E deficient (ApoE−/−) mice with and without AAA were assessed via iTRAQ and analyzed in silico to identify potential circulating markers. Microarray data from ApoE−/− mice and human patients were analyzed in parallel. Phase 2: Putative markers were compared between datasets to shortlist common candidates. Phase 3: The relationship of two shortlisted markers and AAA presence was assessed.
iTRAQ identified eight proteins with biomarker potential. Microarray data identified 72 and 96 potential biomarkers from ApoE−/− mice and human patients, respectively. All three datasets suggested apolipoprotein C1 (ApoC1) as a marker for AAA; microarray data identified matrix metalloproteinase 9 (MMP9) as a second potential marker. Plasma ApoC1 and MMP9 concentrations positively correlated with AAA diameter in ApoE−/− mice.
Clancy, P, Lincz, LF, Maguire, J, McEvoy, M, Koblar, SA & Golledge, J 2014, 'Tenascin-C is increased in atherothrombotic stroke patients and has an anti-inflammatory effect in the human carotid artery.', BioFactors, vol. 40, no. 4, pp. 448-457.View/Download from: UTS OPUS or Publisher's site
Tenascin-C (Tn-C) is an endogenous ligand of toll-like receptor-4 (TLR-4); a key signalling molecule associated with chronic inflammatory conditions. Both Tn-C and TLR-4 are increased in unstable human atheroma, but their effects on local inflammatory conditions have not been investigated. The aim of the present study was to investigate the association and functional implications of Tn-C/TLR-4 signalling in large artery atherosclerotic stroke. Plasma Tn-C was measured by ELISA and found to be higher in recent stroke patients (n = 336; median 12.77 µg/mL, inter-quartile range 10.23-15.74 µg/mL) than in controls (n = 321; median 11.31 µg/mL, inter-quartile range 8.89-13.90 µg/mL), P < 0.001. Plasma Tn-C was also independently positively associated with stroke (odds ratio for highest Tn-C quartile 2.27, 95% confidence interval 1.37-3.76). Assessment of Tn-C associated chronic cytokine secretion was performed in vitro using paired, human, macroscopically disease matched, carotid atheroma tissue biopsies obtained from five patients undergoing carotid endarterectomy. A 4-day incubation with specific Tn-C blocking antibodies (Abs) increased secretion of TLR-4-associated cytokines, interleukin (IL)-8, IL-1β, tumour necrosis factor and C-C motif chemokine (CCL)3 and expression of TLR-4 in the tissue. These results suggest with Tn-C blockade another endogenous TLR-4 ligand upregulates TLR-4 expression and subsequent cytokine secretion. Titration of the Tn-C Abs also dose dependently increased secretion of IL-6, IL-8, IL-1β, and CCL3 in mixed, healthy, primary vascular cell culture. In summary, circulating concentrations of Tn-C are higher in patients with a recent history of atherosclerotic stroke and may play an anti-inflammatory role by reducing pro-inflammatory cytokine release from atheroma.
Cheng, Y-C, Anderson, CD, Bione, S, Keene, K, Maguire, JM, Nalls, M, Rasheed, A, Zeginigg, M, Attia, J, Baker, R, Barlera, S, Biffi, A, Bookman, E, Brott, TG, Brown, RD, Chen, F, Chen, W-M, Ciusani, E, Cole, JW, Cortellini, L, Danesh, J, Doheny, K, Ferrucci, L, Franzosi, MG, Frossard, P, Furie, KL, Golledge, J, Hankey, GJ, Hernandez, D, Holliday, EG, Hsu, F-C, Jannes, J, Kamal, A, Khan, MS, Kittner, SJ, Koblar, SA, Lewis, M, Lincz, L, Lisa, A, Matarin, M, Moscato, P, Mychaleckyj, JC, Parati, EA, Parolo, S, Pugh, E, Rost, NS, Schallert, M, Schmidt, H, Scott, RJ, Sturm, JW, Yadav, S, Zaidi, M, Boncoraglio, GB, Levi, CR, Meschia, JF, Rosand, J, Sale, M, Saleheen, D, Schmidt, R, Sharma, P, Worrall, B & Mitchell, BD 2012, 'Are Myocardial Infarction-Associated Single-Nucleotide Polymorphisms Associated With Ischemic Stroke?', STROKE, vol. 43, no. 4, pp. 980-U143.View/Download from: UTS OPUS or Publisher's site
Holliday, EG, Maguire, JM, Evans, T-J, Koblar, SA, Jannes, J, Sturm, JW, Hankey, GJ, Baker, R, Golledge, J, Parsons, MW, Malik, R, McEvoy, M, Biros, E, Lewis, MD, Lincz, LF, Peel, R, Oldmeadow, C, Smith, W, Moscato, P, Barlera, S, Bevan, S, Bis, JC, Boerwinkle, E, Boncoraglio, GB, Brott, TG, Brown, RD, Cheng, Y-C, Cole, JW, Cotlarciuc, I, Devan, WJ, Fornage, M, Furie, KL, Gretarsdottir, S, Gschwendtner, A, Ikram, MA, Longstreth, WT, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Parati, EA, Psaty, BM, Sharma, P, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, Traylor, M, Verhaaren, BFJ, Wiggins, KL, Worrall, BB, Sudlow, C, Rothwell, PM, Farrall, M, Dichgans, M, Rosand, J, Markus, HS, Scott, RJ, Levi, C & Attia, J 2012, 'Common variants at 6p21.1 are associated with large artery atherosclerotic stroke', NATURE GENETICS, vol. 44, no. 10, pp. 1147-+.View/Download from: UTS OPUS or Publisher's site