Vascular Biology and Medicine

Our research investigates the fundamental mechanisms involved in vascular and myocardial homeostasis and inflammation. We aim to develop new treatments and diagnostics for cardiovascular diseases including coronary heart disease, heart failure, cardiovascular ageing, and microvascular disease.

There is important unmet medical need for an interdisciplinary study of cardiovascular diseases mechanisms, effective identification of therapeutic targets, novel therapeutic regimens, and the development of novel diagnostics and methods of vascular assessment.

Our expertise spans from basic science to clinical medicine. Our strategy is to build bridges among the Newcastle University Institutes and local NHS Trusts. We collaborate with major stakeholders (biotech and pharmaceutical industries) and develop strategies to address major vascular health problems.

Research impact

Our research shows that amyloid-beta levels may be a key indicator of cardiovascular disease. We aim to develop a simple blood test to identify most at-risk patients so that preventative measures can be put in place and death rates reduced.

Our team has explored the formation of senescent cells, also known as zombie cells, in a preclinical model. These cells are damaged and can cause neighbouring cells to become senescent. We have uncovered their formation and identified possible reversal mechanisms to revitalise the heart after a heart attack.

We are investigating exercise capacity in patients with implanted left ventricular assist devices. While the output of blood from the heart improves pressure builds up in the lungs. The pump does not respond to the demands of exercise in the same way as a normal heart.

We have partnered with Kancera AB and secured £1.7M to run the FRACTAL clinical trial. This will test if Kand567, a new drug which blocks Fractalkine, can be used to treat patients after acute myocardial infarction.

We have shown that endoglin is essential for cardiovascular development and maintenance of the adult vasculature. Endoglin is regulated during angiogenesis, and its depletion leads to arteriovenous malformations.

Cardiovascular Immunology

Research topics include:

RNA metabolism and vascular inflammation
T-cell biology in ischemia/reperfusion injury in acute myocardial infarction

Key References

Gladka M, Stellos K.
Scientists on the Spot: RNA modifications in atherosclerosis.
Cardiovascular Research (2021) DOI: 10.1093/cvr/cvaa338

Spray L, Park C, Cormack S, Mohammad A, Panahi P, Boag S, Bennaceur K, Sopova K, Richardson GD, Stangl V, Rech L, Rainer PP, Ramos GC, Hofmann U, Stellos K, Spyridopoulos I.
The fractalkine receptor CX3CR1 links lymphocyte kinetics in CMV-seropositive patients and acute myocardial infarction with adverse left ventricular remodeling.
Frontiers in Immunology (2021) DOI: 10.3389/fimmu.2021.605857

Vlachogiannis NI, Gatsiou A, Silvestris DA, Stamatelopoulos K, Tektonidou MG, Gallo A, Sfikakis PP, Stellos K.
Increased adenosine-to-inosine RNA editing in rheumatoid arthritis.
Journal of Autoimmunity (2020) DOI: 10.1016/j.jaut.2019.102329

Coelho-Lima J, Mohammed A, Cormack S, Jones S, Ali A, Panahi P, Barter M, Bagnall A, Ali S, Young D, Spyridopoulos I.
Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion.
Clinical Chemistry (2019) DOI: 10.1373/clinchem.2019.308353

Leisegang MS, Fork C, Josipovic I, Richter FM, Preussner J, Hu J, Miller MJ, Epah J, Hofmann P, Günther S, Moll F, Valasarajan C, Heidler J, Ponomareva Y, Freiman TM, Maegdefessel L, Plate KH, Mittelbronn M, Uchida S, Künne C, Stellos K, Schermuly RT, Weissmann N, Devraj K, Wittig I, Boon RA, Dimmeler S, Pullamsetti SS, Looso M, Miller FJ Jr, Brandes RP.
Long Noncoding RNA MANTIS Facilitates Endothelial Angiogenic Function.
Circulation (2017) DOI: 10.1161/CIRCULATIONAHA.116.026991

Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jaé N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S.
Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation.
Nature Medicine (2016) DOI 10.1038/nm.4172

Spyridopoulos I, Martin-Ruiz C, Hilkens C, Yadegarfar ME, Isaacs J, Jagger C, Kirkwood T, von Zglinicki T.
CMV seropositivity and T-cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study.
Aging Cell (2016) DOI: 10.1111/acel.12430

Boag SE, Das R, Shmeleva EV, Bagnall A, Egred M, Howard N, Bennaceur K, Zaman A, Keavney B, Spyridopoulos I. T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients.
The Journal of Clinical Investigation (2015) DOI: 10.1172/JCI80055

Cardiovascular Ageing

Research topics include:

amyloid-beta in cardiovascular ageing and disease
senescence in cardiovascular inflammation and ageing
telomere length shortening and telomerase biology

Key references

Lambrinoudaki I, Delialis D, Georgiopoulos G, Tual-Chalot S, Vlachogiannis NI, Patras R, Aivalioti E, Armeni E, Augoulea A, Tsoltos N, Soureti A, Stellos K, Stamatelopoulos K.
Circulating Amyloid Beta 1-40 Is Associated with Increased Rate of Progression of Atherosclerosis in Menopause: A Prospective Cohort Study.
Thrombosis and Haemostasis (2021) DOI 10.1055/s-0040-1721144

Tektonidou MG, Kravvariti E, Vlachogiannis NI, Georgiopoulos G, Mantzou A, Sfikakis PP, Stellos K, Stamatelopoulos K.
Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome. Rheumatology (Oxford) (2021) DOI 10.1093/rheumatology/keaa548

Stakos DA, Stamatelopoulos K, Bampatsias D, Sachse M, Zormpas E, Vlachogiannis NI, Tual-Chalot S, Stellos K.
The Alzheimer's Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar.
Journal of the American College of Cardiology (2020) DOI 10.1016/j.jacc.2019.12.033

Anderson R, Lagnado A, Maggiorani D, Walaszczyk A, Dookun E, Chapman J, Birch J, Salmonowicz H, Ogrodnik M, Jurk D, Proctor C, Correia-Melo C, Victorelli S, Fielder E, Berlinguer-Palmini R, Owens A, Greaves LC, Kolsky KL, Parini A, Douin-Echinard V, LeBrasseur NK, Arthur HM, Tual-Chalot S, Schafer MJ, Roos CM, Miller JD, Robertson N, Mann J, Adams PD, Tchkonia T, Kirkland JL, Mialet-Perez J, Richardson GD, Passos JF.
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.
EMBO (2019) DOI: 10.15252/embj.2018100492

Stamatelopoulos K, Mueller-Hennessen M, Georgiopoulos G, Sachse M, Boeddinghaus J, Sopova K, Gatsiou A, Amrhein C, Biener M, Vafaie M, Athanasouli F, Stakos D, Pateras K, Twerenbold R, Badertscher P, Nestelberger T, Dimmeler S, Katus HA, Zeiher AM, Mueller C, Giannitsis E, Stellos K.
Amyloid-β (1-40) and Mortality in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study. Annals of Internal Medicine (2018) DOI 10.7326/M17-1540

Stamatelopoulos K, Pol CJ, Ayers C, Georgiopoulos G, Gatsiou A, Brilakis ES, Khera A, Drosatos K, de Lemos J, Stellos K.
Amyloid-beta (1-40) peptide and subclinical cardiovascular disease in the general population: the Dallas Heart Study.
Journal of the American College of Cardiology (2018) DOI: 10.1016/j.jacc.2018.06.027

Cardiovascular Therapeutics

Research topics include:

drug discovery and preclinical testing of new therapeutic compounds
clinical trials on patients with cardiovascular disease
development of new surgical interventions

Key references

Maier R, Bawamia B, Bennaceur K, Dunn S, Marsay L, Amoah R, Kasim A, Filby A, Austin D, Hancock H, Spyridopoulos I.
Telomerase Activation to Reverse Immunosenescence in Elderly Patients With Acute Coronary Syndrome: Protocol for a Randomised Pilot Trial.
JMIR Research Protocols (2020) DOI 10.2196/19456

Cormack S, Mohammed A, Panahi P, Das R, Steel AJ, Chadwick T, Bryant A, Egred M, Stellos K, Spyridopoulos I, Capri I.
Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction.
British Journal of Clinical Pharmacology (2020) DOI 10.1111/bcp.14252

Dookun E, Walaszczyk A, Redgrave R, Palmowski P, Tual‐Chalot S, Suwana A, Chapman J, Jirkovsky E, Donastorg Sosa L, Gill E, Yausep O, Santin Y, Mialet‐Perez J, Owens WA, Grieve D, Spyridopoulos I, Taggart M, Arthur HM, Passos JF, Richardson GD.
Clearance of senescent cells during cardiac ischemia–reperfusion injury improves recovery.
Aging Cell (2020) DOI: 10.1111/acel.13249

Zaman A, de Winter R, Kogame N, Chang C, Modolo R, Spitzer E, Tonino P, Hofma S, Zurakowski A, Smits C, Prokopczuk J, Moreno R, Choudhury A, Petrov I, Cequier A, Kukreja N, Hoye A, Iniguez A, Ungi I, Serra A, Gil R, Walsh S, Tonev G, Mathur A, Merkely B, Colombo A, Ijsselmuiden S, Soliman O, Kaul U, Onuma Y, Serruys P.
Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial.
Lancet (2019) DOI 10.1016/S0140-6736(18)32467-X

Windecker S, Latib A, Kedhi E, Kirtane AJ, Kandzari DE, Mehran R, Price MJ, Abizaid A, Simon DI, Worthley SG, Zaman A, Hudec M, Poliacikova P, Abdul Ghapar AKB, Selvaraj K, Petrov I, Mylotte D, Pinar E, Moreno R, Fabbiocchi F, Pasupati S, Kim HS, Aminian A, Tie C, Wlodarczak A, Hur SH, Marx SO, Jankovic I, Brar S, Bousquette L, Liu M, Stone GW; ONYX ONE Investigators.
Polymer-based or polymer-free stents in patients at high bleeding risk: ONYX ONE.
The New England Journal of Medicine (2019) DOI: 10.1056/NEJMoa1910021

Laina A, Gatsiou A, Georgiopoulos G, Stamatelopoulos K, Stellos K.
RNA Therapeutics in Cardiovascular Precision Medicine.
Frontiers in Physiology (2018) DOI: 10.3389/fphys.2018.00953

Aortic and Vascular Disease

Research topics include:

characterize the vascular involvement in amyloidosis and multiple myeloma
understand the mechanism leading to and treatments for aortic aneurysm
study the role of blood vessel, development, formation, and angiogenesis in cardiovascular disease
understand the genetics underlying congenital heart defects
develop novel cardiovascular and microvascular assessment and treatment technologies
understand the causes of vascular dementia and depression in late life

Key references

Allen J, Liu H, Iqbal S, Zheng D, Stansby, G.
Deep learning-based photoplethysmography classification for peripheral arterial disease detection: a proof-of-concept study.
Physiological Measurement (2021) DOI: 10.1088/1361-6579/abf9f3

Kastritis E, Laina A, Georgiopoulos G, Gavriatopoulou M, Papanagnou ED, Eleutherakis-Papaiakovou E, Fotiou D, Kanellias N, Dialoupi I, Makris N, Manios E, Migkou M, Roussou M, Kotsopoulou M, Stellos K, Terpos E, Trougakos IP, Stamatelopoulos K, Dimopoulos MA.
Carfilzomib-induced endothelial dysfunction, recovery of proteasome activity, and prediction of cardiovascular complications: a prospective study.
Leukemia (2021) DOI: 10.1038/s41375-021-01141-4

Tual-Chalot S, Garcia-Collado M, Redgrave RE, Singh E, Davison B, Park C, Lin H, Luli S, Jin Y, Wang Y, Lawrie A, Jakobsson L, Arthur HM.
Loss of Endothelial Endoglin Promotes High-Output Heart Failure Through Peripheral Arteriovenous Shunting Driven by VEGF Signalling.
Circulation Research (2020) DOI: 10.1161/CIRCRESAHA.119.315974

Allen J, O’Sullivan J, Stansby G, Murray A.
Age-related changes in pulse risetime measured by multi-site photoplethysmography.
Physiological Measurement (2020) DOI 10.1088/1361-6579/ab9b67

Nandhra S, Scott E, Boyan L, Williams R, McCaslin J.
The interplay between Preoperative anaemia and post-operative blood transfusion on survival following fenestrated aortic aneurysm repair.
Annals of Vascular Surgery (2020) DOI: 10.1016/j.avsg.2020.06.040

Stamatelopoulos K, Georgiopoulos GA, Athanasouli F, Nikolaou PE, Lykka M, Roussou M, Gavriatopoulou M, Laina A, Trakada G, Charakida M, Delialis D, Petropoulos I, Pamboukas C, Manios E, Karakitsou M, Papamichael C, Gatsiou A, Lambrinoudaki IV, Terpos E, Stellos K, Andreadou I, Dimopoulos MA, Kastritis E.
Reactive Vasodilation Predicts Mortality in Primary Systemic Light Chain (AL) Amyloidosis.
Circulation Research (2019) DOI: 10.1161/CIRCRESAHA.119.314862

Phillips HM, Stothard CA, Shaikh Qureshi WM, Kousa AI, BrionesLeon JA, Khasawneh RR, Sanders R, O'Loughlin C, Mazzotta S, Dodds R, Seidel K, Bates T, Nakatomi M, Cockell SJ, Schneider JE, Mohun TJ, Maehr R, Kist R, Peters H, Bamforth SD.
Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis.
Development (2019) DOI: 10.1242/dev.177618

Bano A, Gan Addison C, Narayanan K, Weaver J, Tsatlidis V, Razvi S.
Age May Influence the Impact of TRAbs on Thyroid Function and Relapse-Risk in Patients with Graves Disease.
The Journal of Clinical Endocrinology & Metabolism (2018) DOI: 10.1210/jc.2018-01738

Theme leadership

Konstantinos Stellos is our Theme Lead. Guy MacGowan, Gavin Richardson and Ioakim Spyridopoulos are the Deputy Theme Leads.

We provide research-led teaching in cardiovascular health and disease at all levels. Ioakim Spyridopoulos is our Education Lead.

Early career researchers interested in collaborating, please contact Sandip Nandhra.

Professional Administration Services are provided by Stephen Allott.

We are a supportive and inclusive community. Our theme EDI lead is Simon Tual-Chalot.

People

Theme lead - Professor Konstantinos Stellos

Staff list

Immune cells contribute to injury after myocardial infarction.

Cultured senescence cell used for drug screening.

Magnetic resonance imaging and pressure and volume loops to study heart function.

Vascular network of the retina.

Dr Esha Singh supporting the BHF at the Great North Run.

All Research Themes