Newcastle University

Roles and Responsibilities

Honorary Consultant Interventional Cardiologist, Freeman Hospital,

Newcastle upon Tyne Hospitals, NHS Foundation Trust

Research Interests

Finding how ageing of stem cells and the immune system affect cardiovascular disease

Endothelial Progenitor Cells in Vascular Repair
Endothelial dysfunction plays a pivotal role for the development and progression of atherosclerosis. Atherogenic risk factors harbor the potential to injure the endothelial layer by promoting
apoptosis, preceded by an inflammatory reaction in the vessel wall. Therefore, the maintenance of the endothelial layer is a crucial process to ensure its integrity. Endothelial repair is also dependent on the capacity of mature endothelial cells to proliferate and migrate. More recent studies suggest an important role of circulating endothelial progenitor cells (EPCs) contributing to reendothelialization after vascular injury by homing to denuded parts of the artery following balloon injury. We have investigated the cellular and molecular biology of EPCs in patients with cardiovascular disease as well as the influence of important metabolic pathways such as AMP-activated protein kinases (AMPK) in vascular repair. Currently we are investigating the role of LKB1, a serine-threonine kinase upstream of AMPK, in EPCs and its potential role in vascular repair.

Stem Cell Ageing and Immunosenescence in Cardiovascular Disease
A very useful marker of ageing is the measurement of telomere length in human cells. Telomeres are TTAGGG DNA repeats at the ends of chromosomes (see inlay: red dots), helping to maintain their integrity. They are widely regarded as the internal biological clock of a living organism, and shorten by a few base pairs with every cell division. Previous studies have found that short telomeres predispose for cardiovascular disease and mortality due to infection. We are using the Flow-FISH technique to measure telomere length by flow cytometry (see inlay 2), which enables us mesure telomere length (TL) in different leukocyte subpopulations as well as in CD34+ stem and progenitor cells. We have demonstrated that TL of CD34+ cells can be derived from TL of peripheral myeloid cells (granulocytes, monocytes). We also found that exhaustion of bone marrow derived stem cells (BMCs) is one feature in patients with severe heart failure and that TL and functional capacity of BMCs are strongly associated. We also published that the TL difference between lymphocytes and granulocytes is increased in patients with previous myocardial infarction when compared to age-matched controls, suggesting accelerated telomere shortening in lymphocytes. Therefore, lymphocytes or a subpopulation of lymphocytes from patients with coronary heart disease seem to have had a higher proliferative activity when compared to healthy individuals. Currently we are investigating a potential link between immunosenescence (ageing of the immune system) and cardiovascular disease. We are also looking into how statins (cholesterol inhibitors) affect telomere biology in lymphocytes and immunosenescence.

Key Publications

Spyridopoulos I, Hoffmann J, Aicher A, Brümmendorf TH, Doerr HW, Zeiher AM, Dimmeler S. Accelerated telomere shortening in leukocyte subpopulations of patients with coronary heart disease: role of cytomegalovirus seropositivity. Circulation. 2009;120:1364-72

Spyridopoulos I, Erben Y, Brummendorf TH, Haendeler J, Dietz K, Seeger F, Kissel CK, Martin H, Hoffmann J, Assmus B, Zeiher AM, Dimmeler S. Telomere gap between granulocytes and lymphocytes is a determinant for hematopoetic progenitor cell impairment in patients with previous myocardial infarction. Arterioscler Thromb Vasc Biol. 2008;28:968-974.

Spyridopoulos I, Fichtlscherer S, Popp R, Toennes SW, Fisslthaler B, Trepels T, Zernecke A, Liehn EA, Weber C, Zeiher AM, Dimmeler S, Haendeler J. Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism. Arterioscler Thromb Vasc Biol. 2008;28:1967-1974.

Spyridopoulos I, Dimmeler S. Can telomere length predict cardiovascular risk? Lancet. 2007;369:81-82.

Spyridopoulos I, Haendeler J, Urbich C, Brummendorf TH, Oh H, Schneider MD, Zeiher AM, Dimmeler S. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation. 2004;110:3136-3142.

Co-workers

Monika Loeher, BSc
Newcastle University Research Associate

Newcastle University PhD students:

Mohsin Wahad 

Nouf Al-Ajmi

• Spyridopoulos I. Is telomerase a potential target for vascular rejuvenation?. Atherosclerosis 2011, 216(1), 19-20.
• Lehmann R, Luxembourg B, Miesbach W, Suess C, Leus M, Lindhoff-Last E, Zeiher AM, Spyridopoulos I. Idiopathic (unexplained) pulmonary embolism is associated with an impaired prognosis compared to other entities of pulmonary embolism. Blood Coagulation & Fibrinolysis 2010, 21(1), 70-76.
• Lehmann R, Fichtlscherer S, Schachinger V, Held L, Hobler C, Baier G, Zeiher AM, Spyridopoulos I. Complete Revascularization in Patients Undergoing Multivessel PCI is an Independent Predictor of Improved Long-term Survival. Journal of Interventional Cardiology 2010, 23(3), 256-263.
• Spyridopoulos I, Hoffmann J, Aicher A, Brummendorf TH, Doerr HW, Zeiher AM, Dimmeler S. Accelerated Telomere Shortening in Leukocyte Subpopulations of Patients With Coronary Heart Disease Role of Cytomegalovirus Seropositivity. Circulation 2009, 120(14), 1364-1372.
• Seeger FH, Chen L, Spyridopoulos I, Altschmied J, Aicher A, Haendeler J. Downregulation of ETS rescues diabetes-induced reduction of endothelial progenitor cells. PLoS ONE 2009, 4(2), e4529.
• Lehmann R, Fichtlscherer S, Schachinger V, Held L, Hobler C, Baier G, Zeiher AM, Spyridopoulos I. Favorable Long-Term Survival in Patients Undergoing Multivessel-PCI Compared to Predicted Prognosis of CABG Estimated by EuroSCORE: Procedural and Clinical Determinants of Long-Term Outcome. Journal of Interventional Cardiology 2009, 22(6), 511-519.
• Lehmann R, Suess C, Leus M, Luxembourg B, Miesbach W, Lindhoff Last E, Zeiher AM, Spyridopoulos I. Incidence, clinical characteristics, and long-term prognosis of travel-associated pulmonary embolism. European Heart Journal 2009, 30(2), 233-241.
• Haendeler J, Drose S, Buchner N, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S. Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage. Arteriosclerosis, Thrombosis, and Vascular Biology 2009, 29(6), 929-935.
• Fischer-Rasokat U, Brenck F, Zeiher AM, Spyridopoulos I. Radial augmentation index unmasks premature coronary artery disease in younger males. Blood Pressure Monitoring 2009, 14(2), 59-67.
• Linzbach S, Samigullin A, Yilmaz S, Tsioga M, Zeiher AM, Spyridopoulos I. Role of N-Terminal Pro-Brain Natriuretic Peptide and Cystatin C to Estimate Renal Function in Patients With and Without Heart Failure. American Journal of Cardiology 2009, 103(8), 1128-1133.
• Hoffmann J, Erben Y, Zeiher AM, Dimmeler S, Spyridopoulos I. Telomere length-heterogeneity among myeloid cells is a predictor for chronological ageing. Experimental Gerontology 2009, 44(5), 363-366.
• Spyridopoulos I, Fichtlscherer S, Popp R, Toennes SW, Fisslthaler B, Trepels T, Zernecke A, Liehn EA, Weber C, Zeiher AM, Dimmeler S, Haendeler J. Caffeine enhances endothelial repair by an AMPK-dependent mechanism. Arteriosclerosis, Thrombosis, and Vascular Biology 2008, 28(11), 1967-1974.
• Spyridopoulos I, Altschmied J, Andres V, Haendeler J. Mitochondrial p27 Is Required For Endothelial Energy Metabolism And Cell Migration. In: Circulation: 81st Annual Scientific Session of the American Heart Association. 2008, New Orleans, LA: Lippincott Williams & Wilkins.
• Jakob S, Schroeder P, Lukosz M, Buchner N, Spyridopoulos I, Altschmied J, Haendeler J. Nuclear Protein Tyrosine Phosphatase Shp-2 Is One Important Negative Regulator of Nuclear Export of Telomerase Reverse Transcriptase. Journal of Biological Chemistry 2008, 283(48), 33155-33161.
• Spyridopoulos I, Erben Y, Brummendorf TH, Haendeler J, Dietz K, Seeger F, Kissel CK, Martin H, Hoffmann J, Assmus B, Zeiher AM, Dimmeler S. Telomere gap between granulocytes and lymphocytes is a determinant for hematopoetic progenitor cell impairment in patients with previous myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology 2008, 28(5), 968-974.
• Honold J, Geiger L, Assmus B, Fischer Rasokat U, Schachinger V, Zeiher AM, Spyridopoulos I. The initial slope of the VCO2/VO2-curve (s1) in cardiopulmonary exercise testing is a strong and independent predictor of outcome in patients with previous myocardial infarction. Clinical Research in Cardiology 2008, 97(12), 882-890.