Institute of Genetic Medicine

Staff Profile

Professor Ioakim Spyridopoulos

Prof of Cardiovascular Gerontology

Background

Roles and Responsibilities

Director of Newcastle University Cardiovascular Research Centre


Honorary Consultant Interventional Cardiologist, Freeman Hospital,

Newcastle upon Tyne Hospitals, NHS Foundation Trust


Cardiovascular Specialty Co-Lead NIHR Clinical Research Network North East and North Cumbria


Fellow of the European Society of Cardiology (FESC)


Research

Our group is interested on the role of the immune system during cardiovascular ageing, such as how the immune system regulates inflammation (“Inflammaging”). Our approach is translational, identifying relevant questions in patients with coronary artery disease and modelling them in the lab. We will translate our results back to the patient through development of pathway-specific drugs.

  

What is the Role of T-lymphocytes in Myocardial ischemia/reperfusion Injury ?

Coronary artery disease is the single largest cause of mortality worldwide, with myocardial infarction being the most serious manifestation. Timely and effective myocardial reperfusion using primary PCI in acute ST elevation myocardial infarction (STEMI) has substantially improved clinical outcomes of patients. Following reopening of the blocked artery, reperfusion itself can cause myocardial injury and cell death (myocardial ischaemia/reperfusion injury). Studies in animal MI models and human therapeutic interventions indicate that ischemia/reperfusion injury is responsible for up to 50% of final infarct size. While CD4 T-lymphocytes (T-cells) have been shown to promote myocardial ischemia/reperfusion injury in the mouse model, their role during STEMI in humans is by large unknown. A low number of lymphocytes following myocardial infarction is a negative predictor of survival, and we have previously shown (PLoS One 2012) that CD4 and CD8 T-cells drop by up to 50% in the peripheral blood during the first 30 min following reperfusion. At the moment we are conducting three BHF and NIHR funded studies to investigate the role of T-cells in myocardial ischemia-reperfusion and peri-infarct inflammation. We have also previously shown (Circulation 2009) that prior infection with cytomegalovirus (CMV) is associated with shorter telomeres of CD8 T-cells in patients with previous myocardial infarction, correlating with left ventricular function. Another aim of our studies is therefore to find out if CMV seropositivity has an impact on peri-infarct inflammation and healing.


  

What is the Role of Telomerase in Atherosclerosis

Atherosclerosis is an age-related systemic disease characterized by systemic oxidative stress and low grade chronic inflammation, mediated by various leukocyte populations. Telomere dysfunction has been implicated in ageing and senescence of different cell types. Shorter leukocyte telomeres, possibly the result of decreased telomerase activity, are also associated with increased cardiovascular risk and mortality. However, so far no mechanistic link on a cellular level has been found between ageing and atherosclerosis. Telomerase as a DNA polymerase principally functions to protect and elongate telomeres; however, we and others have shown additional “non-canonical” effects of telomerase that are potentially of relevance to atherosclerosis. In our current project we aim to investigate whether telomerase could prove to be a decelerator of atherosclerosis by maintaining generation and suppressive function of CD4 regulatory T-cells, potent suppressors of inflammation and atherogenesis.

 

Postdoctoral Fellows

Karim Bennaceur, PhD

 

PhD Students

Lilia Draganova

Jose Coelho Lima Junior


MD Students

Ashfaq Mohammed

 

Collaborators

Thomas von Zglinicki, Institute of Ageing and Health

Gabriele Saretzki, Institute of Ageing and Health

Helen Arthur, Institute of Genetic Medicine

Bill Chaudhry, Institute of Genetic Medicine

Steve Todryk, Northumbria University

Ziad Mallat, Cambridge University

 

 Selected Recent Publications

1. 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. 2015

2. 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.

3. Hoffmann J, Shmeleva EV, Boag SE, Fiser K, Bagnall A, Murali S, Dimmick I, Pircher H, Martin-Ruiz
C, Egred M, Keavney B, von Zglinicki T, Das R, Todryk S, Spyridopoulos I. Myocardial Ischemia and
Reperfusion Leads to Transient CD8 Immune Deficiency and Accelerated Immunosenescence in CMVSeropositive
Patients. Circ Res. 2015;116:87-98.

4. Shmeleva EV, Boag SE, Murali S, Bennaceur K, Das R, Egred M, Purcell I, Edwards R, Todryk S,
Spyridopoulos I. Differences in immune responses between CMV-seronegative and -seropositive
patients with myocardial ischemia and reperfusion. Immun Inflamm Dis. 2015;3:56-70.

5. Spyridopoulos I, Noman A, Ahmed JM, Das R, Edwards R, Purcell I, Bagnall A, Zaman A, Egred M.
Shock-index as a novel predictor of long-term outcome following primary percutaneous coronary
intervention. Eur Heart J Acute Cardiovasc Care. 2015;4:270-277.

6. Spyridopoulos I, von Zglinicki T. Telomere length predicts cardiovascular disease. BMJ.
2014;349:g4373.

7. Hoffmann J, Spyridopoulos I. Senescent cytotoxic T cells in acute myocardial infarction: innocent
bystanders or the horsemen of apocalypse? Cell Mol Immunol. 2015;12:510-512.

8. Fischer-Rasokat U, Honold J, Lochmann D, Liebetrau C, Leick J, Hamm C, Fichtlscherer S, Mollmann
H, Spyridopoulos I. Ivabradine therapy to unmask heart rate-independent effects of beta-blockers on
pulse wave reflections. Clin Res Cardiol. 2014;103:487-494.

9. Al-Ajmi N, Saretzki G, Miles C, Spyridopoulos I. Dietary restriction ameliorates haematopoietic
ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing
phenotype. Exp Gerontol. 2014;58:113-119.

10. Bennaceur K, Atwill M, Al Zhrany N, Hoffmann J, Keavney B, Breault D, Richardson G, von Zglinicki
T, Saretzki G, Spyridopoulos I. Atorvastatin induces T cell proliferation by a telomerase reverse
transcriptase (TERT) mediated mechanism. Atherosclerosis. 2014;236:312-320.




Teaching

I teach in our Universities Masters of Research program "Cardiovascular Science in Health and Disease", as well as Medical students (NC University and Erasmus program)

Publications