Vascular Biology and Medicine
Our research investigates the fundamental mechanisms involved in vascular homeostasis and inflammation. We aim to develop new treatments for
vascular diseases including coronary heart disease
heart failure
cardiovascular ageing
Research highlights
Our research shows amyloid-beta levels may be a key indicator of cardiovascular disease. Our aim is to develop a simple blood test that indicates risk of heart disease.
In a preclinical model our team has explored the formation of senescent – or zombie cells. These cells do not work correctly and can cause others to become senescent. Our team has uncovered how they form and possible reversal mechanisms.
We are investigating exercise capacity in patients with implanted left ventricular assist devices. Whereas the output of blood from the heart improves. Pressure builds up in the lungs as the pump does not respond to the demands of exercise that a normal heart is able to do.
Our members
Our expertise spans from basic science to clinical medicine. We work closely with our local NHS Trusts. We collaborate with the biotech and pharmaceutical industries.
International scientific societies recognise our members. Professor Konstantinos Stellos received the Outstanding Achievement Award 2020. The European Society of Cardiology. In recognition of his work on atherosclerotic cardiovascular disease.
Dr. Aikaterini Gatsiou serves as an Early Career Committee member at the American Heart Association (AHA) Council on Genomic and Precision Medicine. This recognises her groundbreaking research on endogenous RNA nucleotide modifications and inflammatory disease.
We are a supportive and inclusive community. Our theme EDI lead is Simon Tual-Chalot. Early career researchers interested in collaborating please contact Gavin Richardson.
Our current research focuses on the elucidation of the role of:
- biochemical RNA modifications in RNA surveillance and immunovascular communication
- RNA modification enzymes in endothelial cell homeostasis
- amyloid-beta in vascular function and atherosclerotic cardiovascular disease development and prognosis
- RNA therapeutics in the treatment of cardiovascular disease
We demonstrated that adenosine-to-inosine RNA editing is critically involved in arterial vascular diseases. It controls HuR-mediated post-transcriptional regulation of the extracellular matrix degradation enzyme cathepsin S. Our current focus is the role of RNA modifications in vascular homeostasis and disease.
We have collaborated with academic centres in Greece, Germany, Switzerland and USA on amyloid-beta. This pro-inflammatory peptide is key in the development of atherosclerosis. It stratifies patients at correct risk categories. It also predicts mortality in coronary artery disease.
Our aim is to explore the clinical value of amyloid-beta. In both atherosclerotic cardiovascular disease development and prognosis.
Lead: Konstantinos Stellos
Key references
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. J Am Coll Cardiol. 2020 Mar 3;75(8):952-967.
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. J Autoimmun. 2020 Jan;106:102329
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. Circ Res. 2019 Sep 27;125(8):744-758. *Equal senior authorship
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. Ann Intern Med. 2018; 168(12):855-865.
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. J Am Coll Cardiol. 2018; 72:1060-61.
Gatsiou A, Stellos K. Dawn of Epitranscriptomic Medicine. Circ Genom Precis Med. 2018 Sep;11(9):e001927Laina A, Gatsiou A, Georgiopoulos G, Stamatelopoulos K, Stellos K. RNA Therapeutics in Cardiovascular Precision Medicine. Front Physiol. 2018 Jul 25;9:953.
Gatsiou A, Vlachogiannis N, Lunella FF, Sachse M, Stellos K. Adenosine-to-Inosine RNA Editing in Health and Disease. Antioxid Redox Signal. 2018 Sep 20;29(9):846-863.
Understanding the pathophysiology of reperfusion and healing in myocardial infarction including:
- identifying biomarkers of failed reperfusion
- role of inflammation and T cell biology in cardiac remodelling post infarction
- understanding how immune ageing affects the inflammatory response
- developing anti-inflammatory immune therapies to improve remodelling
We've shown that leukocyte subsets expressing the fractalkine receptor CX3CR1 decrease in peripheral and coronary artery blood. This suggests acute marginalisation and transmigration during acute myocardial infarction. This correlates with severity of infarcts and outcome.
CX3CR1 is expressed in virus-specific, pro-inflammatory cytotoxic CD4 and CD8 T-lymphocytes. It also increases with age.
In preclinical models we have demonstrated the role of T-lymphocytes in remodelling. Our aim is to translate these findings to the clinic. The focus would be on clinical trials in patients with acute myocardial infarction.
Lead: Ioakim Spyridopoulos
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 Randomized Pilot Trial. JMIR Res Protoc. 2020;9:e19456.
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. Br J Clin Pharmacol. 2020;86:1387-1397.
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. Clin Chem. 2019; 66:247-256
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;15:389-392.
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. J Clin Invest. 2015;125:3063-3076.
Research in this area includes clinical outcomes with left ventricular assist devices. Including:
- long term outcomes
- myocardial recovery on ventricular assist devices
- mechanisms of exercise intolerance in ventricular assist devices
- special populations such as adult congenital heart disease
We conduct research into exercise and lifestyle interventions for hypertrophic cardiomyopathy. As well as develop novel therapies in muscular dystrophy cardiomyopathies.
Our team investigate the effects of ageing on left ventricular structure and function.
We are developing a novel diagnostic strategy for heart failure. This involves a simple exercise test.
We research novel perfusion methods of donor hearts. Aimed at improving myocardial preservation and increasing the number of donor hearts.
Lead: Guy MacGowan
Key references
Rushton S, Parameshwar J, Lim S, Dar O, Callan P, Al-Attar N, Tsui S, MacGowan GA. The introduction of a super-urgent heart allocation scheme in the UK: a two-year review. Accepted Journal of Heart and Lung Transplantation
Koshy A, Bouzas Cruz N, Okwose NC, Gonzalez Fernandez O, Green T, Woods A, Robinson-Smith N, Tovey S, McDiarmid A, Parry G, Schueler S, Jakovljevic DG, MacGowan GA. Left Ventricular Filling Pressures Contribute to Exercise Limitation in Patients with Continuous Flow Left Ventricular Assist Devices. ASAIO Journal 2020 Mar;66(3):247-252.
Parikh JD, Hollingsworth KG, Wallace D, Blamire A, MacGowan GA. Left Ventricular Functional, Structural and Energetic Effects of Normal Aging: Comparison with Hypertension. PLOS One https://doi.org/10.1371/journal.pone.0177404 May 11, 2017.
Understanding the role of senescence in cardiovascular ageing and disease including:
- age-related heart failure
- myocardial infarction
- atherosclerosis
We have demonstrated that an accumulation of stress-induced senescence contributes to inflammation and myocardial remodelling. This occurs during ageing and following myocardial infarction.
In preclinical models we have eliminated senescence using senolytic compounds. This has reduced inflammation and improved cardiac function in both disease settings. Our aim is now to translate these findings to the clinic.
We also aim to develop a biomarker of age-related cardiovascular disease. We are evaluating senescence and the senescence associated secretory phenotype for this purpose.
Lead: Gavin Richardson
Key references
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 J. 2019.
Dookun E, Walaszczyk A, Redgrave R, Palmowski P, Tual-Chalot S, Suwana A, Chapman J, Jirkovsky E, Sosa LD, Gill E, Yausep OE, 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 heart recovery following myocardial infarction. bioRxiv. 2020:2020.2004.2028.065789.
Martin-Ruiz C, Hoffmann J, Shmeleva E, Zglinicki Tv, Richardson G, Draganova L, Redgrave R, Collerton J, Arthur H, Keavney B, Spyridopoulos I. Cmv-independent increase in cd27−cd28+ cd8+ emra t cells is inversely related to mortality in octogenarians. npj Aging and Mechanisms of Disease. 2020;6:3.
Richardson GD, Sage A, Bennaceur K, Al Zhrany N, Coelho-Lima J, Dookun E, Draganova L, Saretzki G, Breault DT, Mallat Z, Spyridopoulos I. Telomerase mediates lymphocyte proliferation but not the atherosclerosis-suppressive potential of regulatory t-cells. Arterioscler Thromb Vasc Biol. 2018;38:1283-1296.
Walaszczyk A, Dookun E, Redgrave R, Tual-Chalot S, Victorelli S, Spyridopoulos I, Owens A, Arthur HM, Passos JF, Richardson GD. Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction. Aging Cell. 2019:e12945.