Imperial College London

DrAllanKiprianos

Faculty of MedicineNational Heart & Lung Institute

 
 
 
//

Contact

 

+44 (0)20 7594 2728a.kiprianos

 
 
//

Location

 

ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

8 results found

Khan E, Ambrose N, Ahnstrom J, Kiprianos A, Stanford M, Eleftheriou D, Brogan P, Mason J, Johns M, Laffan M, Haskard Det al., 2016, A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s Syndrome, Clinical and Experimental Rheumatology, Vol: 6, ISSN: 1593-098X

Thrombosis is common in Behçet’s Syndrome (BS), and there is a need for better biomarkers for risk assessment. As microparticles expressing Tissue Factor (TF) can contribute to thrombosis in preclinical models, we investigated whether plasma microparticles expressing Tissue Factor (TF) are increased in BS. We compared blood plasma from 72 healthy controls with that from 88 BS patients (21 with a history of thrombosis (Th+) and 67 without (Th−). Using flow cytometry, we found that the total plasma MP numbers were increased in BS compared to HC, as were MPs expressing TF and Tissue Factor Pathway Inhibitor (TFPI) (all p < 0.0001). Amongst BS patients, the Th+ group had increased total and TF positive MP numbers (both p ≤ 0.0002) compared to the Th- group, but had a lower proportion of TFPI positive MPs (p < 0.05). Consequently, the ratio of TFPI positive to TF positive MP counts (TFPI/TF) was significantly lower in Th+ versus Th− BS patients (p = 0.0002), and no patient with a TFPI/TF MP ratio >0.7 had a history of clinical thrombosis. We conclude that TF-expressing MP are increased in BS and that an imbalance between microparticulate TF and TFPI may predispose to thrombosis.

Journal article

Khan E, Ambrose N, Ahnstrom J, Kiprianos A, Stanford M, Eleftheriou D, Brogan P, Mason J, Johns M, Laffan M, Haskard Det al., 2016, A LOW BALANCE BETWEEN MICROPARTICLES EXPRESSING TISSUE FACTOR PATHWAY INHIBITOR AND TISSUE FACTOR IS ASSOCIATED WITH THROMBOSIS IN BEHCET'S SYNDROME, Publisher: CLINICAL & EXPER RHEUMATOLOGY, Pages: S143-S143, ISSN: 0392-856X

Conference paper

Bauer A, Mylroie H, Thornton C, Calay D, Birdsey G, Kiprianos A, Wilson GK, Soares MP, Yin X, Mayr M, Randi A, Mason JCet al., 2016, Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis, Scientific Reports, Vol: 6, ISSN: 2045-2322

Angiogenesis is an essential physiological process and an important factor in diseasepathogenesis. However, its exploitation as a clinical target has achieved limited success and novelmolecular targets are required. Although heme oxygenase-1 (HO-1) acts downstream of vascularendothelial growth factor (VEGF) to modulate angiogenesis, knowledge of the mechanismsinvolved remains limited. We set out identify novel HO-1 targets involved in angiogenesis. HO-1depletion attenuated VEGF-induced human endothelial cell (EC) proliferation and tube formation.The latter response suggested a role for HO-1 in EC migration, and indeed HO-1 siRNA negativelyaffected directional migration of EC towards VEGF; a phenotype reversed by HO-1 overexpression.EC from Hmox1-/- mice behaved similarly. Microarray analysis of HO-1-depleted andcontrol EC exposed to VEGF identified cyclins A1 and E1 as HO-1 targets. Migrating HO-1-deficient EC showed increased p27, reduced cyclin A1 and attenuated cyclin-dependent kinase 2activity. In vivo, cyclin A1 siRNA inhibited VEGF-driven angiogenesis, a response reversed by AdHO-1.Proteomics identified structural protein vimentin as an additional VEGF-HO-1 target. HO-1depletion inhibited VEGF-induced calpain activity and vimentin cleavage, while vimentin silencingattenuated HO-1-driven proliferation. Thus, vimentin and cyclins A1 and E1 represent VEGFactivatedHO-1-dependent targets important for VEGF-driven angiogenesis.

Journal article

Hamdulay SS, Wang B, Calay D, Kiprianos AP, Cole J, Dumont O, Dryden N, Randi AM, Thornton CC, Al-Rashed F, Hoong C, Shamsi A, Liu Z, Holla VR, Boyle JJ, Haskard DO, Mason JCet al., 2014, Synergistic therapeutic vascular cytoprotection against complement- mediated injury induced via a PKC alpha-, AMPK-, and CREB- dependent pathway, Journal of Immunology, Vol: 192, Pages: 4316-4327, ISSN: 1550-6606

Endothelial injury and dysfunction precede accelerated arterial disease in allograft vasculopathy and systemic autoimmune diseases and involve pathogenic Abs and complement. Recent reports suggest that switching to rapamycin from calcineurin antagonists reduces posttransplant vasculopathy and prolongs survival following cardiac transplantion. The majority of these patients also receive statin therapy. We examined potential mechanisms underlying this protective response in human endothelial cells and identified synergy between rapamycin and atorvastatin. Mechanistically, atorvastatin and rapamycin activated a protein kinase Cα, AMP-activated kinase, and CREB-dependent vasculoprotective pathway, which induced decay-accelerating factor (DAF) promoter activity via binding to the cAMP response element, mutation of which attenuated promoter activity. This response significantly increased endothelial cell surface DAF and enhanced protection against complement-mediated injury. Synergy with rapamycin was reproduced by simvastatin, whereas combining atorvastatin with cyclosporine or mycophenolate in place of rapamycin was ineffective. Importantly, synergy was reproduced in vivo, in which only atorvastatin and rapamycin therapy in combination was sufficient to induce DAF on murine aortic endothelium. We believe this pathway represents an important therapeutically inducible vasculoprotective mechanism for diseases mediated by pathogenic Abs and complement, including posttransplant vasculopathy and systemic lupus erythematosus. Although our study focuses on the vascular endothelium, the findings are likely to be broadly applicable, given the diverse cellular expression of DAF.

Journal article

Kiprianos AP, Morgan MD, Little MA, Harper L, Bacon PA, Young SPet al., 2012, Elevated active secretory sphingomyelinase in antineutrophil cytoplasmic antibody-associated primary systemic vasculitis, ANNALS OF THE RHEUMATIC DISEASES, Vol: 71, Pages: 1100-1102, ISSN: 0003-4967

Journal article

Kiprianos AP, Morgan MD, Little MA, Savage COS, Harper L, Bacon PA, Young SPet al., 2011, Elevated active secretory acid sphingomyelinase activity in ANCA-AAV, 15th International Vasculitis/ANCA Workshop, Publisher: WILEY-BLACKWELL, Pages: 134-135, ISSN: 0009-9104

Conference paper

Rauf K, Kiprianos AP, Bacon PA, Young SPet al., 2010, COX-2 INHIBITION ENHANCES BRADYKININ-INDUCED CALCIUM SIGNALLING IN ENDOTHELIAL CELLS, Annual Meeting of the British-Society-Rheumatology/Spring Meeting of British-Health-Professional-in-Rheumatology, Publisher: OXFORD UNIV PRESS, Pages: I44-I45, ISSN: 1462-0324

Conference paper

Kiprianos AP, Church LD, Little M, Savage CO, Bacon PA, Young SPet al., 2010, SERUM ACID SPHINGOMYELINASE AS A MARKER AND MEDIATOR OF VASCULAR DAMAGE, Annual Meeting of the British-Society-Rheumatology/Spring Meeting of British-Health-Professional-in-Rheumatology, Publisher: OXFORD UNIV PRESS, Pages: I122-I123, ISSN: 1462-0324

Conference paper

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00792550&limit=30&person=true