Cardiff Met University Projects
ROX medical Cerebral Blood Flow study 2018
Cardiff Metropolitan University
Cardiff &Vale UHB
B. J McDonnell (PI)
J. Coulson (Co-I)
Cockcroft (Co-I)
ROX medical
Understanding the impact of arteriovenous shunt implantation on aortic blood pressure and cerebrovascular blood flow.
AIM-HY INFORM: 2017-2018
Cardiff Metropolitan University
Cardiff & Vale UHB
Kings College London
University of Cambridge
B. J McDonnell (Co-I)
J. Coulson (Co-I)
Chowienchyzk (CI)
I.B Wilkinson (PI)
MRC/BHF
MRC/BHF funded multi-centre clinical trial investigating the effects of ethnicity on efficacy of different anti-hypertensive therapy.
ARCADE Trial (Assessment of Respiratory Complications and Airways Disease Evaluation. 2016-2019
Cardiff Metropolitan University
Cardiff University
B. McDonnell (PI)
N. Gale (Co-I)
GlaxoSmithKline
Longitudinal observational trial investigating the impact of arterial stiffness on cerebral blood flow in patients with Chronic Obstructive Pulmonary Disease.
“HIT-LVAD” Trial, 2016-2019 Haemodynamics Informing Treatment in patients implanted with Left Ventricular Assist Devices.
Cardiff Metropolitan University
Cardiff University
B. McDonnell (PI)
E J Stohr (Fellow)
J Willey (Co-I)
P Colombo (Co-I)
Horizon2020, Marie Sklodowska-Curie, Global Fellowship,
Haemodynamics Informing treatment in heart failure patients implanted with Left Ventricular Assist Devices (HIT-LVAD). Marie Sklodowska Curie Action grant, investigating the impact of mechanical circulatory support on cerebrovascular haemodynamics.
Anglo-Cardiff Collaborative Trial (ACCT)
Cardiff Metropolitan University
University of Cambridge
B McDonnell (PI) Cardiff
Cockcroft (Co-I)
McEniery (PI) Cambridge
Wilkinson IB (CI)
BHF
Population based study, investigating the mechanisms associated with vascular ageing and hypertension.
Anglo-Cardiff Collaborative Trial (ACCT)
Cardiff Metropolitan University
University of Cambridge
B McDonnell (PI) Cardiff
Cockcroft (Co-I)
McEniery (PI) Cambridge
Wilkinson IB (CI)
BHF
Population based study, investigating the mechanisms associated with vascular ageing and hypertension.
The influence of sex hormones and exercise training in the regulation of cerebrovascular blood flow and reactivity during adolescence
Cardiff Metropolitan University
Dr Mike Stembridge (PI). Dr Jon Oliver, Dr Chris Pugh
Internally funded studentship- CSSHS £60k
To examine the relationship between maturation, physical activity and neurovascular regulation in young boys and girls to explore the health-related benefits of exercise during adolescence, and how this can shape our cognitive function.
Collaborative links: Professor Philip Ainslie, UBCO: https://hes.ok.ubc.ca/person/philip-ainslie-2/ and Dr Ali McManus UBCO: https://hes.ok.ubc.ca/person/ali-mcmanus/
The role of hypoxia-inducible factors in the regulation of cerebral blood flow in hypoxia.
Cardiff Metropolitan University
Professor Philip Ainslie (PI). Dr Mike Stembridges
Canadian Research Chair in Cerebrovascular Physiology, an NSERC Discovery Grant.
NSERC postgraduate scholarship.
Conclusion: Although low flow supplemental O2 does not alter volumetric gCBF in COPD patients, the increased SpO2 results in improved cerebral oxygen delivery and neurovascular function. This improvement in cerebral oxygen delivery and neurovascular function with supplemental O2 may underscore the cognitive benefits, and reduced risk of cognitive impairment associated with O2 therapy in COPD. Collaborative links: Professor Philip Ainslie, UBCO:
https://hes.ok.ubc.ca/person/philip-ainslie-2/
Stroke Research and Innovation Network.
Cardiff Metropolitan University
James PE, Freeman A, Davies R, Hewitt J.
Stroke Implementation Group/HCRW (2017-2019)
Stroke is one of the top three causes of death and the leading cause of adult disability in Wales. The Welsh Government recognises that a comprehensive, cross-sector, stroke-specific, collaborative research strategy is needed to harness the opportunities offered in Wales, creating an ambitious and innovative research environment. This takes advantage of an infrastructure in Wales that has developed to facilitate world-leading research and innovation in the prevention, diagnosis, and treatment of Stroke. The establishment of a “Hub” as a recognised point of contact was considered critical to implementation of the Government 5 year Stroke strategy. It is also clear that a Coordinator/Manager role was key to coordinate activities and to set up and maintain a cross-Wales Network. To this end, the Stroke Implementation Group agreed to fund a Manager/Coordinator from funds made available from Welsh Government. The aims are to support Research, Innovation and Education in Stroke across Wales.
Cell-derived microparticles as mediators of obesity-induced vascular disease. (2015-2018)
Cardiff Metropolitan University /Cardiff University
Rees, DA and James PE
Royal College of Physicians Fellowship
58% of adults in Wales are classified as overweight or obese which puts them at higher risk of diabetes, cardiovascular disease and various malignancies. Adipocytes constitute the largest endocrine tissue and secrete a variety of molecules causing increased inflammation and immune dysfunction in obese patients. In recent years the role of cell-derived vesicles (Extracellular vesicles, or EVs) as horizontal messengers between the donor and the target cells has been increasingly recognised. However, the mechanism by which EVs affect the intercellular signalling is still being debated. As EVs have been shown to induce endothelial dysfunction in patients with metabolic syndrome, this project will characterise EV-mediated signalling pathways between adipose tissue and vascular endothelium. As obesity is a critical risk factor and a pre-requisite to cardiovascular disease, modulating these pathways may have huge potential therapeutic application. We postulate that circulating EVs reflect the increased inflammatory status in obese patients and are involved in the development of endothelial dysfunction which may be evident already in individuals with increased BMI who haven’t developed full metabolic syndrome yet and/or its clinical consequences.
Extracellular vesicle transport in the circulation – a missing link between adipocytes and accelerated vascular dysfunction
(2015-2018)
Cardiff Metropolitan University /Cardiff University
James PE, Rees DA, Clayton A, O-Donnell VB,
British Heart Foundation Project Grant
Using in vitro models, we confirmed that fat cells release microscopic-sized particles called extracellular vesicles into their external environment. In conditions reflecting obesity (a setting whereby fat cells are oxygen-starved and inflamed), the vesicles released were found to be both smaller in size and in greater abundance, than those released under healthy conditions. Vesicles from oxygen-starved and inflamed fat cells also contained different levels of certain messenger molecules (hormone-like chemicals that affect other cells and tissues). When introduced to cells that line blood vessels, this increased the abundance of certain proteins on their cell surface known to affect the sticking of cells, and in tests resulted in white blood cells sticking to the blood vessel wall.
Importantly, we also developed techniques during the course of this study that have provided evidence that vesicles released from fat cells are present in the human circulation.
Can we prevent generation of pro-thrombotic and pro-coagulant extracellular microvesicles generation in blood via a simple dietary intervention? (2014-2018)
Cardiff Metropolitan University /Cardiff University
Rees DA, James PE
NIHSCR PhD Studentship
This project will increase our knowledge on the mechanisms implicated in the development and progression of atherosclerosis, and will test a novel potential treatment for coronary heart disease. Extracellular vesicles (EV) are emerging as potential biomarkers for coronary heart disease and are attractive targets for dietary and/or pharmacological intervention. This proposal will delineate which EV characteristics are associated with cardiovascular risk triggers. Our contention is that dietary nitrite/nitrate supplementation will reduce the formation of damaging blood-borne EVs, leading to a potential new approach for early intervention and chronic disease management.
Measurement of pathologically relevant microvesicle populations in obesity-driven cardiovascular disease (2015-2018)
Cardiff Metropolitan University / Cardiff University
James PE, Rees DA
College of Biomedical and Life Sciences International PhD Scholarship
The cross disciplinary research grouping at Cardiff has established state-of-the-art methods for EV assessment. Recent work has focussed on the identification and characterization of EVs from adipose tissue and their adverse effect on vascular and circulatory function. The occurrence of adipocyte-derived EV in the human circulation is a novel finding recently proposed by the James research group. Moreover, the influence of adipocyte derived EV on other prevalent EV populations (platelet, endothelial and T cell) in humans has not been tested. Of particular relevance to this PhD project they adopted an approach of targeting a combination of markers which are selective for an adipocyte lineage (FABP4 and PPARy2) and have recently piloted ELISA-based methodology that allows the measurement of protein EV components both on the EV surface and within. The overall aim of this PhD will be to fully develop ELISA-based measurement of EV populations within blood samples that can (1) specifically label MV origin, (2) accurately quantify relevant MV populations, (3) enable high-throughput assessment, and (4) be applied to investigate obesity-driven effects on the circulation.
Effect Of Thienopyridines And Non-Thienopyridines On Endothelial Dysfunction And NO Metabolites (2013-2018)
Cardiff Metropolitan/Cardiff and Vale University Health Trust
James PE, Anderson RA
Nott Legacy Thrombosis Research Fund
Clopidogrel is a commonly prescribed antiplatelet drug with significant variation in partial antiplatelet response in patients. Blockage of the P2Y12 receptor is considered a major mechanism of its action, however there is evidence that it also exhibits additional and alternate pleiotropic effects which involve formation of stable nitric oxide metabolites in the circulation. This project tests the hypothesis that Clopidogrel antiplatelet effectiveness will be enhanced with dietary supplementation of inorganic nitrate. The primary outcome will be improvement of antiplatelet reactivity of Clopidogrel with oral ingestion of in-organic nitrate. The secondary outcome will be increase in production of R-SNO species in blood of coronary artery disease patients. Patients are recruited from the Cardiac Day case unit (UHW) who are listed for an elective coronary intervention. The dietary nitrate formulation (and corresponding placebo) has been supplied by Science in Sport.
Cardiff Metropolitan University – Top Stroke- related Publications
Hoiland RL, Mladinov S, Barak OF, Willie CK, Mijacika T, Stembridge M, Dujic Z, Ainslie PN (2018). Oxygen therapy improves cerebral oxygen delivery and neurovascular function in hypoxemic chronic obstructive pulmonary disease patients. In review.
Bain AR, Ainslie PN, Hoiland RL, Barak OF, Drvis I, Stembridge M, MacLeod DM, McEneny J, Stacey BS, Tuaillon E, Marchi N, Fayd’Herbe De Maudave A, Dujic Z, MacLeod DB, and Bailey DM (2017). Competitive apnea and its effect on the human brain: focus on the redox-regulation of blood–brain barrier permeability and neuronal–parenchymal integrity. FASEB. doi: 10.1096/fj.201701031R
Fluck D, Morris L, Niroula S, Tallon C, Sherpa K, Stembridge M, Ainslie PN and McManus A (2017). UBC-Nepal Expedition: Markedly lower cerebral blood flow in high altitude Sherpa children compared to children residing at sea-level. J Appl Physiol (1985), Jun 1: doi: 10.1152/japplphysiol.00292.2017.
Hoiland R, Bain AR, Tymko MM, Rieger MG, Howe CA, Willie CK, Hansen AB, Fluck D, Wildfong KW, Stembridge M, Subedi P, Anholm JD and Ainslie PN (2017). Adenosine receptor dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans. J Appl Physiol (1985), Jan 12:jap 00840.2016.
Bain AR, Ainslie PN, Hoiland RL, Barak OF, Cavar M, Drvis I, Stembridge M, MacLeod DM, Bailey DM, Dujic Z & Macleod DB (2016). Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia. J Physiology Sep 15;594(18):5317-28.
Kerley CP, Dolan E, James PE, Cormican L. (2018). Dietary nitrate lowers ambulatory blood pressure in treated, uncontrolled hypertension: a 7-d, double-blind, randomised, placebo-controlled, cross-over trial. Br J Nutr.;119(6):658-663. doi: 10.1017/S0007114518000144.
Burnley-Hall N, Abdul F, Androshchuk V, Morris K, Ossei-Gerning N, Anderson R, Rees DA, James PE. (2018). Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study. Thromb Haemost. ;118(1):112-122. doi: 10.1160/TH17-06-0394.
Burnley-Hall N, Willis G, Davis J, Rees DA, James PE. (2017). Nitrite-derived nitric oxide reduces hypoxia-inducible factor 1α-mediated extracellular vesicle production by endothelial cells.Nitric Oxide. 28;63:1-12. doi: 10.1016/j.niox.2016.12.005.
Kerley CP, O’Neill JO, Reddy Bijjam V, Blaine C, James PE, Cormican L. (2016).
Dietary nitrate increases exercise tolerance in patients with non-ischemic, dilated cardiomyopathy-a double-blind, randomized, placebo-controlled, crossover trial.J. Heart Lung Transplant.35(7):922-6. doi: 10.1016/j.healun.2016.01.018.
Freeman PM, Moschonas KE, Hinz C, O’Donnell VB, Kinnaird TD, James PE, Anderson RA. (2015).
Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients.
Atherosclerosis. 243(1):320-7. doi: 10.1016/j.atherosclerosis.2015.09.024.
Castagna F, Stöhr EJ, Pinsino A, Cockcroft JR, Willey J, Reshad Garan A, Topkara VK, Colombo PC, Yuzefpolskaya M, McDonnell BJ. The Unique Blood Pressures and Pulsatility of LVAD Patients: Current Challenges and Future Opportunities. Curr Hypertens Rep. 2017 Oct 18;19(10):85. doi: 10.1007/s11906-017-0782-6. Review.
Castagna F, McDonnell BJ, Stöhr EJ, Yuzefpolskaya M, Trinh PN, Topkara VK, Garan AR, Flannery MA, Takeda K, Takayama H, Naka Y, Demmer RT, Wassertheurer S, Cockcroft JR, Colombo PC. Noninvasive measurement of peripheral, central and 24-hour blood pressure in patients with the heartmate 2 continuous-flow left ventricular assist device. J Heart Lung Transplant 2017; 36(6):694-697.
Sharman JE, Avolio AP, Baulmann J, Benetos A, Blacher J, Blizzard CE, Boutouyrie P, Chen CH, Chowienczyk P, Cockcroft JR, Cruickshank JK, Ferreira I, Ghiadoni L, Hughes A, Jankowski P, Laurent S, McDonnell BJ, Eniery CM, Millasseau SC, Papaioannou TG, Parati G, Park JB, Protogerou AD, Roman MJ, Schillaci G, Segers P, Stergiou GS, Tomiyama H, Townsend RR, Van Bortel LM, Wang J, Wassertheurer S, Weber T, Wilkinson IB, Vlachopoulos C. Validation of non-invasive central blood pressure devices: ARTERY Society task force consensus statement on protocol standardization. European Heart Journal (2017). (0),1–10. doi:10.1093/eurheartj/ehw632.
McDonnell BJ, Pearson J and Cockcroft JR. Reflections on Vascular Ageing and Microvascular Pulsatility. J Hypertens. 2014. Sep; 32(9):1907-8.
McEniery CM, McDonnell BJ, So A, Aitken S, Bolton CE, Munnery M, Hickson SS, Yasmin, Maki-Petaja KM, Cockcroft JR, Dixon AK, Wilkinson IB; Anglo-Cardiff Collaboration Trial Investigators. Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals. Hypertension. 2009 Mar;53(3):524-31. Epub 2009 Jan 26.