Imperial College London

Dr Charis Pericleous

Faculty of MedicineNational Heart & Lung Institute

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2728c.pericleous Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

142 results found

Noble H, Crossette-Thambiah C, Odho Z, Karawitage N, Logan K, Pericleous C, Laffan M, Arachchillage DJet al., 2023, Frequency and Clinical Significance Anti-PS/PT Antibodies in Patients with Antiphospholipid Syndrome - Single Centre Observational Study in the United Kingdom, SEMINARS IN THROMBOSIS AND HEMOSTASIS, Vol: 49, Pages: 553-557, ISSN: 0094-6176

Journal article

Lang M, Leung K-Y, Greene N, Malone K, Saginc Giannoustas G, Randi A, Kiprianos A, Maughan R, Pericleous C, Mason Jet al., 2023, The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism, Frontiers in Immunology, Vol: 14, Pages: 1-16, ISSN: 1664-3224

Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium.Methods: Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels.Results: In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites.Conclusion: We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium.

Journal article

Farina N, Abdulsalam R, McDonnell T, Pericleous C, D'Souza A, Ripoll VM, Webster J, Isenberg DA, Giles I, Rahman Aet al., 2023, Antiphospholipid antibody positivity in early systemic lupus erythematosus is associated with subsequent vascular events, RHEUMATOLOGY, Vol: 62, Pages: 2252-2256, ISSN: 1462-0324

Journal article

Arachchillage DJ, Pericleous C, 2023, Evolution of Antiphospholipid Syndrome, SEMINARS IN THROMBOSIS AND HEMOSTASIS, Vol: 49, Pages: 295-304, ISSN: 0094-6176

Journal article

Ćorović A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jørgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JMet al., 2023, Somatostatin receptor PET/MR imaging of inflammation in patients with large vessel vasculitis and atherosclerosis., Journal of the American College of Cardiology, Vol: 81, Pages: 336-354, ISSN: 0735-1097

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macropha

Journal article

Arachchillage DJ, Laffan M, Pericleous C, 2023, Hydroxychloroquine as an Immunomodulatory and Antithrombotic Treatment in Antiphospholipid Syndrome, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 24

Journal article

Jayakody Arachchillage D, Rajakaruna I, Pericleous C, Nicolson PLR, Makris M, Laffan M, the CA-COVID-19 Study Groupet al., 2022, Autoimmune disease and COVID-19- a multicentre observational study in the United Kingdom, Rheumatology, Vol: 61, Pages: 4643-4655, ISSN: 1462-0324

ObjectiveTo establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) in comparison to a propensity matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK.MethodsThis is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a pre-designed standardised case record form. Adult patients (≥18 years) admitted between 1st of April 2020 and 31 July 2020 were included.ResultsOverall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with systemic lupus erythematosus, rheumatoid arthritis or antiphospholipid syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia: 240(60.91%) vs 206(52.28%), p= 0.015, raised LDH 150(38.08%) vs 43(10.92%), p< 0.001 and raised creatinine 122(30.96%) vs 86(21.83%), p= 0.01 respectively. A significantly higher proportion of patients with severe rheumatologic AD had raised CRP : 77(96.25%) vs 70(87.5%), p= 0.044 and LDH 20(25%) vs 6(7.5%), p= 0.021. Patients with severe rheumatologic AD had significantly higher mortality [32/80(40%)] compared with propensity matched cohort of patients without AD [20/80(25%)], p= 0.043. However, there was no difference in 180-day mortality between propensity matched cohorts of patients with or without AD in general, p= 0.47.ConclusionsPatients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and raised LDH were more frequent in patients with any AD whilst raised CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19.

Journal article

Hartley A, Greene M, Caga-Anan M, Owen S, Mullin M, Pericleous C, Scott C, Mason J, Haskard DO, Khamis Ret al., 2022, Molecular imaging of experimental atherosclerosis using anti-malondialdehyde-modified low-density lipoprotein humanised antibody fragment targeted nanoparticles, Publisher: OXFORD UNIV PRESS, Pages: 3040-3040, ISSN: 0195-668X

Conference paper

Peverelli M, Porter A, Malone K, Kiprianos A, McKinnon T, Pericleous C, Maughan R, Mason Jet al., 2022, Active Takayasu Arteritis Is Associated with Plasma and Cellular Measures of Endothelial Dysfunction, Publisher: WILEY, Pages: 4425-4427, ISSN: 2326-5191

Conference paper

Kabir L, Maughan R, Paschalaki K, Randi A, Carling D, Arachchillage D, Mason J, Pericleous Cet al., 2022, Evidence for Mitochondrial Dysfunction in Blood-derived Endothelial Colony Forming Cells Isolated from Patients with Antiphospholipid Syndrome, Publisher: WILEY, Pages: 4515-4516, ISSN: 2326-5191

Conference paper

Maughan R, Porter A, Dahanayake C, Ianonne C, Alapat R, Pericleous C, Youngstein T, Mason Jet al., 2022, Evaluating the Safety and Factors Associated with Treatment Cessation in Takayasu Arteritis, Publisher: WILEY, Pages: 4568-4569, ISSN: 2326-5191

Conference paper

McDonnell T, Amarnani R, Spicer C, Jbari H, Pericleous C, Spiteri VA, Wincup C, Artim-Esen B, Mackie I, Botto M, Rahman A, Giles Iet al., 2022, Antibodies to FXa and thrombin in patients with SLE differentially regulate C3 and C5 cleavage, LUPUS SCIENCE & MEDICINE, Vol: 9, ISSN: 2053-8790

Journal article

Hartley A, Greene M, Caga-Anan M, Owen S, Mullin M, Pericleous C, Scott C, Mason J, Haskard D, Khamis Ret al., 2022, IN VIVO WHOLE-BODY FLUORESCENCE MOLECULAR IMAGING OF EXPERIMENTAL ATHEROSCLEROSIS USING ANTI-MALONDIALDEHYDE-MODIFIED LOW-DENSITY LIPOPROTEIN HUMANISED ANTIBODY FRAGMENT TARGETED NANOPARTICLES, Publisher: BMJ PUBLISHING GROUP, Pages: A153-A154, ISSN: 1355-6037

Conference paper

Willis R, McDonnell TCR, Pericleous C, Gonzalez EB, Schleh A, Romay-Penabad Z, Giles IP, Rahman Aet al., 2022, PEGylated Domain I of Beta-2-Glycoprotein I Inhibits Thrombosis in a Chronic Mouse Model of the Antiphospholipid Syndrome, FRONTIERS IN IMMUNOLOGY, Vol: 13, ISSN: 1664-3224

Journal article

Khawaja A, Maughan R, Paschalaki K, Pericleous C, Mason J, Nelson M, Taylor G, Randi A, Boffito M, Emerson Met al., 2022, People living with HIV have higher frequencies of circulating endothelial colony-forming cells: steps towards patient-specific models to evaluate cardiovascular risk, Publisher: WILEY, Pages: 39-39, ISSN: 1464-2662

Conference paper

Crossette-Thambiah C, Pericleous C, Asmar N, Bomsztyk J, Ranger A, Shlebak A, Ramji S, Banerjee S, Laffan M, Jayakody Arachchillage Det al., 2022, Clinical and biological features of cerebral venous sinus thrombosis following ChAdOx1 nCov-19 vaccination, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 93, Pages: 445-448, ISSN: 0022-3050

Vaccines for COVID-19were developed with unprecedented speedand since January 2021, the AstraZeneca/Oxford University ChAdOx1 nCoV-19 vaccine has been administered to over 400 million people globally1. In April 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA)reported a possible association between ChAdOx1 nCoV-19 and a rare syndrome of unusual site thrombosis combined with thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT).Frequency of VITT varies across age groups. Overall 411 cases of VITT have been reported to Medicine & Healthcare prodcuts Regulatory Agency (MHRA) by 21st of July 2021 with fatality rate of 17.76% (73/411)2.

Journal article

Paschalaki K, Rossios C, Pericleous C, MacLeod M, Rothery S, Donaldson G, Wedzicha J, Gorgoulis V, Randi A, Barnes Pet al., 2022, Inhaled corticosteroids reduce senescence in endothelial progenitor cells from COPD patients, Thorax, Vol: 77, ISSN: 0040-6376

Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonarydisease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC),we have demonstrated accelerated senescence in smokers and COPD patients compared tonon-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence(Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damageresponse (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. Invitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICSon the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protectivemolecular mechanism of action of corticosteroids on endothelium.

Journal article

Maughan R, Lang M, Olsson A, Porter A, Greeves A, Youngstein T, Pericleous C, Mason Jet al., 2021, Endothelial Cells from Patients with DMARD Naive, Active Inflammatory Arthritis Demonstrate Pro-inflammatory Sensitisation That Is Reversed by Therapy Initiation, Publisher: WILEY, Pages: 74-76, ISSN: 2326-5191

Conference paper

Benjamin LA, Paterson RW, Moll R, Pericleous C, Brown R, Mehta PR, Athauda D, Ziff OJ, Heaney J, Checkley AM, Houlihan CF, Chou M, Heslegrave AJ, Chandratheva A, Michael BD, Blennow K, Vivekanandam V, Foulkes A, Mummerya CJ, Lunn MP, Keddie S, Spyer MJ, Mckinnon T, Hart M, Carletti F, Jager HR, Manji H, Zandi MS, Werring DJ, Nastoulik E, Simister R, Solomon T, Zetterberg H, Schott JM, Cohen H, Efthymiou Met al., 2021, Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study, ECLINICALMEDICINE, Vol: 39

Journal article

McDonnell T, Amarnani R, Spiteri V, Spicer C, Pericleous C, Artim-Esen B, Mackie I, Botto M, Rahman A, Giles Iet al., 2021, Molecular Modelling Predicts Inhibition of Functional Effects of Anti-thrombin III on Factor Xa Mediated Complement Activation by Anti-Factor Xa IgG in SLE and APS, Publisher: WILEY, Pages: 3147-3148, ISSN: 2326-5191

Conference paper

Porter A, Maughan R, Pericleous C, Kiprianos A, Jee H, Lee P, Youngstein T, Mason Jet al., 2021, Investigating Adenosine Deaminase 2 Activity in Large Vessel Vasculitis, Publisher: WILEY, Pages: 3903-3905, ISSN: 2326-5191

Conference paper

Ahmetaj-Shala B, Marei I, Kawai R, Rothery S, Pericleous C, Mohamed N, Gashaw H, Bokea K, Samuel J, Vandenheste A, Shala F, Kirkby N, Mitchell Jet al., 2021, Activation and contraction of human ‘vascular’ smooth muscle cells grown from circulating blood progenitors, Frontiers in Cell and Developmental Biology, Vol: 9, Pages: 1-6, ISSN: 2296-634X

Blood outgrowth smooth muscle cells offer the means to study vascular cells without the requirement for surgery providing opportunities for drug discovery, tissue engineering and personalised medicine. However, little is known about these cells which has meant their therapeutic potential remains unexplored. Our objective was to investigate for the first time the ability of blood outgrowth smooth muscle cells and vessel derived smooth muscle cells to sense the thromboxane mimetic U46619 bymeasuring intracellular calcium elevation and contraction. U46619 (10 26 -6M) increased cytosolic calcium in blood outgrowth smooth muscle cells fibroblasts. Increased calcium signal peaked between 10-20 seconds after U46619 in both smoothmuscle cell types. Importantly, U46619 (10-9 to 10-6M) induced concentration-dependent contractions of both blood outgrowth smooth muscle cells and vascular smooth muscle cells but not in fibroblasts. In summary, we show that functional responses of blood outgrowth smooth muscle cells are in line with vascular smooth muscle cells providing critical evidence of their application in biomedical research.

Journal article

Liakou P, Maughan R, Pericleous C, Mason P, Mason JCet al., 2021, META-ANALYSIS OF 17 CLINICAL TRIALS USING OMEGA-3 FATTY ACIDS IN PATIENTS WITH CARDIOVASCULAR DISEASE, Publisher: ELSEVIER IRELAND LTD, Pages: E291-+, ISSN: 0021-9150

Conference paper

Ramirez GA, Mackie I, Nallamilli S, Pires T, Moll R, Pericleous C, Isenberg DA, Cohen H, Efthymiou Met al., 2021, Anti-protein C antibodies and acquired protein C resistance in SLE: novel markers for thromboembolic events and disease activity?, RHEUMATOLOGY, Vol: 60, Pages: 1376-1386, ISSN: 1462-0324

Journal article

Khawaja AA, Maughan RT, Paschalaki KE, Taylor KA, Lovell AO, Pericleous C, Mason JC, Randi AM, Boffito M, Emerson Met al., 2020, Modelling endothelial function in vitro and via blood sampling to evaluate cardiovascular risk in people living with HIV, Publisher: WILEY, Pages: 39-39, ISSN: 1464-2662

Conference paper

Khawaja AA, Chong DLW, Sahota J, Mikolasch TA, Pericleous C, Ripoll VM, Booth HL, Khan S, Rodriguez-Justo M, Giles IP, Porter JCet al., 2020, Identification of a Novel HIF-1α-α<sub>M</sub>β<sub>2</sub> Integrin-NET Axis in Fibrotic Interstitial Lung Disease, FRONTIERS IN IMMUNOLOGY, Vol: 11, ISSN: 1664-3224

Journal article

Khawaja AA, Maughan RT, Paschalaki KE, Taylor KA, Lovell AO, Pericleous C, Mason JC, Randi AM, Boffito M, Emerson Met al., 2020, Modelling endothelial function in vitro and via blood sampling to assess cardiovascular risk in people living with HIV, Publisher: JOHN WILEY & SONS LTD, Pages: 105-105

Conference paper

McDonnell TCR, Farinha F, Pericleous C, Griffin M, Nicolaides A, Croca S, Giles I, Rahman Aet al., 2020, ANTI-DOMAIN I POSITIVITY IN SLE AT DIAGNOSIS IS PREDICTIVE OF ATHEROSCLEROTIC PLAQUE DEVELOPMENT, Annual Conference of the British-Society-for-Rheumatology (BSR), Publisher: OXFORD UNIV PRESS, ISSN: 1462-0324

Conference paper

Khawaja AA, Chong DLW, Sahota J, Pericleous C, Ripoll VM, Booth HL, Khan S, Rodriguez-Justo M, Giles IP, Porter JCet al., 2020, Identification of a novel HIF-1α-α<sub>M</sub>β<sub>2</sub> Integrin-NETosis axis in fibrotic interstitial lung disease

<jats:title>Abstract</jats:title><jats:p>Neutrophilic inflammation correlates with mortality in fibrotic interstitial lung disease (ILD) however, the underlying mechanisms remain unclear. We aimed to determine whether aberrant neutrophil activation is a feature of ILD and the relative role of hypoxia. We used lung biopsies and bronchoalveolar lavage (BAL) from ILD patients to investigate the extent of hypoxia and neutrophil activation in lungs of patients with ILD. We complemented these findings with <jats:italic>ex vivo</jats:italic> functional studies of neutrophils from healthy volunteers to determine the effects of hypoxia. We demonstrate for the first time HIF-1α staining in neutrophils and endothelial cells in ILD lung biopsies. Hypoxia enhanced both spontaneous and phorbol 12-myristate 13-acetate (PMA)-induced neutrophil extracellular trap (NET) release (NETosis), neutrophil adhesion, and trans-endothelial migration. Hypoxia also increased neutrophil expression of the α<jats:sub>M</jats:sub> and α<jats:sub>X</jats:sub> integrin subunits. Interestingly, NETosis was induced by α<jats:sub>M</jats:sub>β<jats:sub>2</jats:sub> integrin activation and prevented by cation chelation. Finally, NETs were demonstrated in the BAL from ILD patients, and quantification showed significantly increased cell-free DNA content and MPO-citrullinated histone H3 complexes in ILD patients compared to non-ILD controls. Our work indicates that HIF-1α upregulation may augment neutrophil recruitment and activation within the lung interstitium through activation of β<jats:sub>2</jats:sub> integrins. Our results identify a novel HIF-1α-Integrin-NETosis axis for future exploration in therapeutic approaches to fibrotic ILD.</jats:p>

Journal article

McDonnell T, Wincup C, Buchholz I, Pericleous C, Giles I, Ripoll V, Cohen H, Delcea M, Rahman Aet al., 2020, The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS, BLOOD REVIEWS, Vol: 39, ISSN: 0268-960X

Journal article

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