BHF Centre for Vascular Regeneration

Working together to repair damaged hearts

The Edinburgh-led British Heart Foundation Centre for Vascular Regeneration (CVR), headed up by Professor Andrew Baker, is a collaboration between the University of Edinburgh, the University of Bristol, Imperial College London and King’s College London. The Centre is funded from 2017 – 2021 by the British Heart Foundation’s Mending Broken Hearts campaign.

The British Heart Foundation also funded the first phase of the Centre, a collaboration between Edinburgh, Bristol and King’s, from 2013 – 2017.

The current research is carried out by a multidisciplinary team, comprising cardiologists, cardiac surgeons and basic scientists with expertise in regenerative medicine and vascular biology.

Background to the CVR

Ischaemic heart disease (IHD) is the leading cause of death worldwide, accounting for over 17 million deaths annually (1). The mortality from acute myocardial infarction (MI) has improved significantly and in the United Kingdom 70% or more of the 188,000 patients who suffer from MI each year survive. Modern treatments for chronic angina, involving epicardial coronary artery revascularisation or bypass by percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) respectively, are also very effective. The major challenge, however, is the management and treatment of patients who develop chronic heart failure (CHF) in the weeks, months and years after MI due to progressive left ventricular (LV) remodelling. The incidence of ischaemic CHF has reached epidemic proportions, accounting for an estimated 26 million people worldwide and resulting in more than 1 million hospital episodes annually in the USA and Europe (2). These patients have poor life expectancy and around 20% do not survive past one year. For end-stage ischaemic CHF the mortality rate is about 50% by 5 years, accounting for 70,000 annual deaths in the UK (3, 4). Although there are several medical and device therapies that make a modest impact on this mortality, CHF is an inexorable and largely irreversible condition that is in desperate need of new preventive and therapeutic approaches (5).

References

1. Organistation WH. Global Health Observatory data repository ‘Mortality and global health estimates’ 2008 [http://apps.who.int/gho/data/node.home#. 

2. Ambrosy A, et al. JACC. 2014;63(12):1123-33. 

3. Coleman M, F et al. The Lancet. 2011;377(9760):127-38. 
4. Townsend N, et al. Cardiovascular Disease Statistics: British Heart Foundation; 2014. 
5. Yancy C, J et al. Circulation. 2013;62(16):147-239.

Mission of the CVR

The Centre will focus specifically on therapies that target neovascularization and improved infarct repair early after MI. We will identify the most effective treatments, both by studying the mechanisms by which they modulate tissue-resident and circulating cells during myocardial revascularisation and repair, and by studying their phenotype and function in large animal models of MI that more closely represent the human condition. Moreover, strategies to activate endogenous mechanisms associated with neovasculogenesis, and via recruitment of circulating endothelial progenitors to promote repair both directly and by paracrine signals, may offer bona fide clinical benefit.

Aims and Objectives of the CVR

Theme 1: Exploration of endogenous endothelial origin, fate and plasticity post-MI. Theme 2: Studies to define novel exogenous endothelial mechanisms and therapies. Theme 3: Research defining the origin and plasticity of mesenchymal cells post-MI. Theme 4: Testing three GMP-compatible therapeutic strategies in the pig acute MI model for cardiovascular repair.

Theme 1: Activation of endogenous vascular regeneration

PIs:  Randi, Brittan (co-leads), Mills, Shah, Baker, Mayr, Henderson.

1. To identify the transcriptional and epigenetic pathways underlying the regenerative function of circulating progenitor cells (BOEC).

2. To define endogenous EC pathways promoting neovascularisation and regeneration.

3. To provide in vitro and in vivo functional validation of EC regeneration pathways.

Theme 2: Exogenous vascular regeneration

PIs: Emanueli (lead) Baker, Henderson, Mayr.

1. Investigate the therapeutic potential of established hESC-EC in rodent MI.

2. Promote arterial and lymphatic specification of hESC-EC and assess the impact of transplanted hESC-AEC and -LEC on post-MI vascular regeneration.

3. Investigate the contribution of EV to the therapeutic responses to hESC-ECs.
4. Develop bioinspired synthetic exosomes as off-the-shelf therapeutics to induce vascular regeneration in the setting of MI.

Theme 3: Targeting the cardiac mesenchyme to drive regeneration post-MI

PIs: Henderson, Madeddu (co-leads) Mayr, Shah.

1. Investigate the functional phenotype of cardiac mesenchymal cell subpopulations in health and disease giving rise to vascular smooth muscle cells (VSMC) or fibroblasts.
2. Identify and characterise the pro-reparative mesenchymal subpopulations post-MI using a single cell RNA sequencing approach (scRNA-seq) and subsequent functional testing.
3. Use ECM proteomics to identify the key extracellular cues and paracrine signals regulating mesenchymal cell differentiation in regeneration.

Theme 4: Clinical translation by evaluation of therapies for vascular regeneration

PIs: Ascione, Mills (co-leads), Madeddu, Shah, Baker

1. To study the survival and efficacy of human vascular-targeted stem cell therapies in an advanced porcine model of acute MI at the Translational Biomedical Research Centre (Bristol) operating at NHS and GLPMA standards

Structure of the CVR

Contact us

Enquiries about the Edinburgh-led Centre for Vascular Regeneration can be directed to Gillian Joyce, CVR Research Project Coordinator.

Email: Gillian.Joyce@ed.ac.uk Telephone: +44 (0)131 242 9332

Address: Centre for Cardiovascular Sciences, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ

Research-specific enquires can be directed to the relevant Principal Investigator.

Cross-centre collaboration

The British Heart Foundation also funds an Oxbridge-led Centre for Regenerative Medicine and an Imperial-led Cardiovascular Regenerative Medicine Centre.

A joint symposium of the 3 Centres of Regenerative Medicine is held annually, enabling cross-centre collaboration.