Young Investigator Prize
Winner: Donna Page (University of Manchester)
Identification of the major genetic contributors to Tetralogy of Fallot
Runners-up: Naveed Akbar (University of Oxford), Sonali Munshaw (University of Oxford), Betty Raman (University of Oxford)
Best-of-the-Best Oral Abstract Prizes
Winner: Neil Dufton (Imperial College London)
Endothelial-specific Erg deletion leads to dramatic reduction in cardiopulmonary function
Runner-Up: Simon Tual-Chalot (Newcastle University)
Poster Abstract Prizes
Francesca Bartoli-Leonard (Manchester Metropolitan University)
Loss of Sirt1 in diabetes enhances DNA damage and reduces MRN complex activation resulting in increased vascular calcification
Blanca Tardajos Ayllon (University of Sheffield)
C-rel drives atherosclerosis at sites of disturbed flow by activating imflammatory and proliferative transcriptional programmes in endothelium
A report by Francesca Bartoli-Leonard
Division of Translational Cardiovascular Science, Centre for Biomedicine, Manchester Metropolitan University
The Asia-Pacific Vascular Biology Organisation (APVBO) Meeting was held at Sun Yat-Sen University in the metropolitan city of Guangzhou in the Guandong province of China, on the 9-12th May 2019. This meeting draws together both academic and research-leading international experts from around the globe, ranging from the US, Finland and Australia, and is one of the key meetings within the Pacific region that allows cutting edge research and techniques within the vascular field to be discussed.
As a PhD student with a background in immunology working on vascular calcification within the cardiovascular group in Manchester Metropolitan University, it was exciting to hear about the recent advances in distinguishing the differentiation patterning of both endothelial and smooth muscle cells, highlighting endothelial-to mesenchymal transition (Endo-MT). APVBO are among the few vascular biology conferences offering the breadth of talks focusing on the relationship and distinction between the lymphatic and vascular systems. With angiogenesis at the forefront of most vascular meetings these days, it was interesting to hear it applied in not only the concept of diabetic retinopathy, but also in interesting and unique pathologies such as cerebral cavernous malformations (CCM) and arteriovenous malformations (AVM), superbly discussed by both Professor Wang Min of Yale and Professor Rong Wang from UCSF respectively.
There were many talks regarding the metabolic control of angiogenesis that were insightful, but Dr Hodivala-Dilke was outstanding due to her work on the novel role of Focal Adhesion Kinase (FAK) in increasing endothelial and fibroblast proliferation. She convincingly demonstrated that increased FAK expression reduces chemo-sensitivity in both breast and pancreatic cancer patients and that the loss of FAK solely within the endothelial cell compartment of a tumour was able reduce tumour growth via increasing susceptibility to DNA damaging chemo-therapies, possibly negating the need for multiple invasive surgeries if utilised correctly. This talk was brilliantly complemented by Professor Yihai Cao’s work from the Karolinska Institute, where he discussed the role of antiangiogenic cancer therapy and the mechanistic challenges and clinical implications that follow. Interestingly, Professor Yihai noted that whilst more recently anti-cancer drugs have been in concordance with anti-angiogenesis treatments, there has been little success in the translation to the clinic, compared to the comparatively good results generated with pre-clinical models. He stressed that, whilst we are still far from fully understanding the mechanisms in which anti-angiogenic medications work in cancer treatment, better prediction markers must be identified if we are to notably target earlier prevention and improve patient outcomes in the future.
Cell heterogeneity and differentiation were also hot topics at this conference, with much discussion focusing on endothelial heterogeneity following vascular injury and inflammation. Doctor Jalees Rehman of The University of Illinois College of Medicine spoke in depth on the understanding of tissue specific molecular signatures, using single cell RNA-seq to identify novel sub-populations of endothelial cells, with distinct functions. Furthermore, he discussed at great length the comparative use of FACS sorting compared to the RiboTag model, the latter of which utilises a pulldown method in which he demonstrated a 0% contamination level with other cell types, compared to negatively sorting FACS, in which cells may get wrongly sorted, decreasing clustering accuracy and blurring our understanding of the precise inflammatory profile these sub-populations gain following injury. Moreover, the RiboTag method allows the mice to be crossed with cell type specific Cre recombinase, and expression of the epitope tagged protein is activated in the cell type of interest only, instead of having to isolate the organ beforehand, reducing the time taken from harvesting to sequencing.
Finally, I would like to thank the BSCR for awarding me this travel grant which allowed me to attend this interesting and educational event and visit a culturally enriching part of the world, and that I would never have had the opportunity to go to otherwise. This meeting was superbly conducted from start to finish and has greatly expanded my knowledge not only in the basic science of the vasculature, but also expanded my translational knowledge in a wide range of pathologies. I had the opportunity to participate in many interesting and in-depth discussions, and with the knowledge gained and connections made during this meeting, I look forward to continuing my research into this cutting edge field in the future.
A report by Gavin McClean
EuroPrevent, soon to be renamed ESC Preventative Cardiology, is the leading international congress on preventive cardiology, organised by the European Association for Preventative Cardiology (EAPC), and was held in Lisbon, Portugal from 11-13th April 2019. Attendance at this conference provided the opportunity to attend over 60 scientific sessions, over 3 days of scientific exchange, offering the prospect of meeting over 1400 healthcare professionals from over 50 countries, in addition to 165 international expert faculty members.
As a congress on preventive cardiology, symposiums ranged from ‘Management of the elderly frail patient in cardiac rehabilitation’ to ‘Protecting the stars of tomorrow – Cardiac imaging strategies in the paediatric athlete’. Symposiums ranged in style, from traditional presentations to case-based discussions on imaging in athletes, wherein, speakers discussed cases presented at their clinic, with members of the audience invited to provide their opinion on further diagnostic test evaluations and diagnosis of disease via a quiz format. Presentations, therefore, offered both a formal and practical learning experience, that is freely available to review at https://esc365.escardio.org/ until Wednesday, 10 July 2019.
As a soon to be Ph.D. graduate, exploring the effect of physical growth, biological maturation and ethnicity on cardiac pre-participation screening in male paediatric athletes, presentation of my findings in a moderated poster examination, was a fantastic opportunity. This session provided a platform for personal development, facilitated by the opportunity to speak to international investigators in person, enabling me to seek their advice and review innovative ideas, whilst establishing international collaborations where possible.
As a Young Ambassador of the EAPC, recently elected Young Ambassador Representative in the EAPC 2018-2020 Membership Committee and Young Community Core Group, attendance at this conference allowed me to both maintain and build upon European collaborations within the field of Preventative Cardiology. Furthermore, as per my role in the Membership Committee, attendance at this conference facilitated my contribution to the development of the EAPC community.
Attendance at EuroPrevent 2019 was not limited to presentations and discussions led by world experts, but also presented a unique opportunity to meet and engage with peers and international experts through a variety of social events. Namely, the Young Community Cocktails attended not only by young investigators but also by established members of the faculty. Furthermore, Young investigators were encouraged to attend the young community open meeting, providing the opportunity to meet and engage with fellow peers on ideas to raise awareness and promote preventative cardiology within attendees’ respective countries, whilst also meeting the editor in chief of the European Journal of Preventative Cardiology. The Young Community is an ever growing new endeavour of the EAPC, with members of our LinkedIn group increasing year on year, boasting over 350 members and a newly formed Facebook group.
Finally, I would like to express my gratitude to the British Society for Cardiovascular Research for their support in allowing me to travel to this international congress.
Department of Bioengineering, Imperial College London
The 8th Biennial Heart Valve Biology & Tissue Engineering Meeting was held in the Royal Society of Medicine, London, UK on 26th to 28th September 2018. This meeting is one of a few specialised and multi-disciplinary meetings that gathers experts from different fields, including biologists, engineers, material scientists, and clinicians, to share and discuss their latest discoveries in valve development and cell biology, pathogenesis of valve calcification, and tissue engineered valves.
As a PhD student working on shear stress-mediated atherogenesis, I have always been interested in exploring how blood fluidic shear stress can play a role in other diseases. Heart valves continuously experience a highly dynamic mechanical environment; hence I am interested in learning more about heart valve mechanobiology and this meeting served as a good venue for me to learn from and to meet experts from the field.
There were a few talks on the mechano-pathology of heart valve calcification that appealed to me. Alan Lam from Professor Craig Simmons’ lab in the University of Toronto, Canada, gave a talk on mechanically directed osteogenesis of valve interstitial cells (VIC) mediated by FHL2-RhoA signaling. Porcine aortic VIC cultured on stiffer collagen-coated silicone (23 kPa) formed more osteogenic aggregates with increased RhoA activation and increased FHL2 nuclear localization as compared to a softer counterpart (7 kPa). This might explain why calcified aortic valve lesions form preferentially in the natively stiffer fibrosa side of the valve leaflet. Nicolas Villa-Roel from Hanjoong Jo’s lab in Georgia Institute of Technology and Emory University, USA, presented his work on the role of miR-483 in shear-induced aortic valve endothelial dysfunction and calcification. He showed that miR-483 is a novel shear-sensitive miRNA in human aortic valve endothelial cells and that it regulates endothelial inflammation, endothelial-to-mesenchymal transition, and valve calcification by inhibiting Ube2c and the HIF1α pathway. miR-483 can be further investigated to explore its therapeutic potential in valve calcification.
Another highlight of this meeting was the debate between Professor Simon Hoerstrup from Wyss Zurich and Technical University Eindhoven, and Professor Ulrich Stock from the Royal Brompton Hospital on the topic of “Do tissue engineered heart valves need to be viable implants?” Professor Hoerstrup, who was on the proposition side, briefed us on the importance of developing viable implants (implantable valves with live cells) that can be implanted into children and adapt to the growth of the patients. He had also reaffirmed that, although viable implants are complex and logistically demanding, that should not be stopping the scientists from developing it because not very far in the future, viable implants could be achievable and affordable for every patient. On the opposition side, Professor Stock disputed the need for a viable implant because of the complexity and cost of making a viable valve for patients. He also emphasized the current urgent need of a simple, ‘foolproof’, cost-effective, and quick solution for patients who are currently suffering from heart valve disease.
On the last day of the meeting, I had the opportunity to interview one of the organizing committee, Dr Adrian Chester, who is a deputy director of research from The Magdi Yacoub Institute and an honorary senior research fellow from National Heart & Lung Institute, Imperial College London. He told me that “The motivation of this meeting is to give a forum for young investigators to present their work in a meeting that is quite intimate and focused on a relatively narrow subject but an expanding field and to give them a chance to meet those established figures in the field. A lot of other valve meetings are dominated by clinical aspects of valve treatment, and the basic science of valve biology is potentially swamped by the clinical discussion. There is no other focused meeting on valve biology and tissue engineering like this one. Heart valve calcification and disease is an entity in itself that offers many interesting questions to address. Knowledge in other cardiovascular diseases is not directly transferable to valve calcification. It is a very important area to investigate because there are a lot of people with valve disease. It is a major cardiovascular entity that deserves and requires basic research,” added Dr Chester. Dr Chester also urged those who are having a research interest in the basic science of valve biology and tissue engineering to contact him.
Last but not least, I would like to thank BSCR for the travel award which contributed towards my expenses. This meeting was an eye-opener and it expanded my knowledge of cardiovascular diseases. I have also had many thought-provoking discussions with experts in the field. I hope that with the knowledge and connections that I have gained from this meeting, I am able to expand my research expertise in the future by venturing into this field of research.
Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen
The 22nd Annual Meeting of the Scottish Cardiovascular Forum (SCF) was held on February 2nd 2019, at The Centre for Health Science in Inverness and was hosted by the University of the Highlands and Islands.
The meeting focused on a wide variety of cardiovascular subjects including blood flow, heart failure, and atherosclerotic plaque formation. The welcoming and encouraging atmosphere of the SCF Annual Meeting makes it a great setting for early career scientists to learn and share ideas.
The key-note speaker, Professor Damian Bailey, head of the Neurovascular Research Laboratory at the University of South Wales, opened the meeting by discussing oxygen supply to the brain. In his address, he discussed the adaptive capacity of our brains to overcome episodes of extremely low levels of oxygen.
After this stimulating kick off, the nominated early stage PhD students competed for the award for the best three-minute oral PhD presentation. The varied topics included modulators of heart failure, new digital tools and interventions for clinicians, aortic valve stenosis, and pulmonary hypertension.
After the early stage PhD talks, Dr Mark MacAskill from the University of Edinburgh presented his work on developing a novel preclinical model of atherosclerotic plaque microcalcification. His approach on plaque imaging can reveal intraplaque microcalcification using in vivo and ex vivo Positron Emission Tomography imaging. Next, Dr Guy Bewick from the University of Aberdeen explained his work on baroreceptor activity and its potential as a drug treatment to reduce hypertension.
During the lunchbreak there was time for the conference poster session. A broad range of topics and techniques were covered on the posters, leading to engaging discussions between the presenters and the audience. After the lunchbreak, it was time for the final year PhD students competing for the Roger Wadsworth prize for Best Presentation. At the start of the session, Professor Ian Megson from the University of the Highlands and Islands gave a brief speech outlining the life, successes, and inspiring academic legacy of Professor Wadsworth who worked at the University of Strathclyde for most of his academic life. The nominated final year PhD presenters covered a wide variety of topics with talks on cardiac remodelling during the development of acute heart failure known as Takotsubo syndrome, cell proliferation observed in pulmonary hypertension, oral microbiome and the effects of dietary nitrate supplementation, and links between diabetes and cardiovascular disease. The nominees were Nadine Godsman from the University of Aberdeen, Andrew McNair from Glasgow Caledonian University, Mia Burleigh from the University of the West of Scotland, and Maria Luisa Fiorello from the University of the Highlands and Islands. It was my pleasure to have also been nominated to present my PhD project research during this session. My presentation focussed on a novel protein target to reduce plaque formation and lipid deposition in experimental atherosclerosis. By knockout of the protein called phosphoprotein enriched in astrocytes (PEA-15) in ApoE knockout mice, plaque formation is reduced, despite an increased body weight gain owing to a high fat diet. This results from an increased efficiency in lipid storage in the adipose tissue, protecting the mice from lipid deposition in the arterial wall and liver. This project is supported by the British Heart Foundation.
The subsequent session of Oral Communications was opened by Dr Junxi Wu (University of Edinburgh) presenting his research to engineer blood vessels using a cell moulding method with human vascular smooth muscle cells and fibroblasts. Mr Tanguy Bléhaut (University of Edinburgh) spoke about his work on utilizing the atheroprotective properties of H2S using TST knockout mice. Next, Richard Lightbody, PhD student from Glasgow Caledonian University presented his work on identifying miRNA sequences during the process of foam cell formation. Finally, Dr Nimesh Mody (University of Aberdeen) presented his research on inhibition of the ceramide biosynthesis during the development of atherosclerosis using fenretinide treatment.
Closing off a day of talks and posters, was the award ceremony during which Dr Moira Wadsworth, Professor Roger Wadsworths’ wife, presented the prize for the best final year PhD presentation. I was happily surprised when I was called forward to accept the prize, even more so because all talks were excellent and well presented by my colleagues! Um-May Sumya, PhD student from the Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, received the prize for best three-minute presentation in the category for early PhD students. Her PhD research has found that restricting dietary zinc led to reduced platelet aggregation and delayed clot growth in blood samples of healthy volunteers. The SCF poster prize was awarded to Dr James Hislop and Dr Dawn Thompson (University of Aberdeen) for their poster presentation of their work on dampening pro-inflammatory mechanisms to promote tissue repair, mainly through activation of the G protein-coupled receptor called formyl peptide receptor 2. The prize in the final category, best presenter during the Oral Communications, was awarded to Tanguy Bléhaut (University of Edinburgh). The abstracts of all of the presentations and posters will be published in a supplement of the BMJ’s Heart journal.
Finally, I would like to extend my thanks to the Wadsworth family and the organizing committee members of the SCF event for an informative and great day. Next year’s Annual Meeting will be held at the University of Strathclyde, so keep an eye out for updates on www.scf.strath.ac.uk.
The International Society for Heart Research (ISHR) is seeking applications for a distinguished award of international importance for recognizing outstanding young scientists: The Richard J Bing Young Investigator Award. The monetary prize is $1,500 for the winner of the Richard J Bing Award and $1,000 for 3 runner-up Finalists. This high-profile recognition will be presented at the XXIIIth ISHR World Congress in Beijing, China, June 3-6, 2019. The Winner and Finalists will be announced in the Journal of Molecular and Cellular Cardiology (the official publication of the ISHR), on the ISHR website, and in Heart News and Views (the newsletter of the ISHR).
The guidelines should be consulted before preparing any application.
As detailed in the relevant guidelines on the ISHR website, all nomination materials should be provided in electronic format, as a SINGLE PDF file either via email or on a flash drive. If you do not get a confirming e-mail within one week, please send a follow-up inquiry without the attached files.
Applications/Nominations should be submitted (by email, mail/airmail or courier) to BOTH:
Dr Åsa Gustafsson
Chair – Bing Award Selection Committee
Skaggs School of Pharmacy and Pharmaceutical Sciences
University of California San Diego
9500 Gilman Drive #0758
La Jolla, CA 92093-0758
Email: [email protected]
Dr Leslie Anderson Lobaugh
ISHR Executive Secretary
PO Box 52643
Durham, NC 27717-2643
Email: [email protected]
Melbourne Convention & Exhibition Centre Melbourne, Australia
A report by Worrapong Kit-Anan
The Stevens, Terracciano and Harding laboratory
Department of Materials, Bioengineering, Myocardial Function
Imperial College London, UK
A great excitement in regenerative medicine drew a gigantic attention from both researchers and the public when scientists can reprogram somatic cells into pluripotent stem cells. This novel technology holds a great promise in a range of applications including cardiac repairs, disease modelling and drug discovery.
The ISSCR Annual Meeting 2018 is the biggest and most prestigious international conference in stem cell society and brings together global leading researchers and innovators on all aspect of stem cell for the future of medicine and research. Topics of discussion ranged from biomaterials for tissue regeneration and disease modelling, epigenetics and genetic regulatory networks, and clinical translation session. This allows participants to engage in cross-disciplinary dialogue and exchange of ideas. This episode of the annual meeting was held in Melbourne Convention & Exhibition Centre Melbourne, Australia.
My research project focuses on cardiac biology for a better understanding of physical cues that essentially play roles during cardiac development. My research addresses the significant challenges present due to the complex and dynamic interplay of electrical and biomechanical signals involved in the development and physiology of the myocardium. The study involves interdisciplinary techniques from synthetic biology, polymer synthesis and cardiac electrophysiology. This requires cross-disciplinary expertise and state of art techniques. Thus, the field is very dynamic as new techniques are continuously being innovated for an application.
My personal highlights were the tissue engineering session and cardiac development and disease, chaired by Professor Matthias Lutolf and Professor Charles Murry, respectively. Memorable talks in tissue engineering were given by Dr Kiryu Yap and Professor Gordana Vunjak-Novakovic. Dr Yap’s talk was related to a novel vascularisation technique that he recently published, which utilises our body’s repair mechanism to form an extensive vascular network in a scaffold. He then explanted the scaffold that had been vascularised for further application. This technique potentially allows scientists to create more relevant regenerative scaffold allowing healthy integration with the human body. This talk was followed by Professor Vunjak-Novakovic. She presented her recent works in cardiac tissue engineering and extracellular vesicles (EVs). The study used dynamic mechanical stimulation synchronously with electrical stimulation to create cardiac sheet made of human induce pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The microtissue showed promisingly many adult-like features such as microstructure and force generation. EVs is an emerging area of great excitement in cell biology and signalling involves the release and subsequent uptake of membrane enclosed packages of information. She presented EVs that has been isolated from hiPSC-CMs in comparison to hiPSC can rescue cardiac function after myocardial infarction, having a cardiac protective effect.
Another concurrent session, cardiac development and disease, featured many renown leading scientists includes Professor Christine L. Mummery and Professor Deepak Srivastava. Professor Mummery presented her current work on organ-on-a-chip and microtissue solutions in which co-culture technique was used with a mixture of cardiomyocytes, cardiac vascular and stromal cells were presented. She introduced novel differentiation technique in which those earlier mentioned cell types were derived spontaneously single in vitro, showing improvement in structural and functional maturity. The group combined with new methods for functional phenotyping to quantify the outcomes of drug and disease mutation responses in situ. Next session was featured by professor Srivastava, introducing his novel direct reprogramming of resident fibroblasts for cardiac regeneration. By using his novel technique, cardiomyocytes can re-enter cell cycle allowing them to undergo cell division.
Finally, I am very grateful for the opportunity that BSCR gave me to go to this conference and expand my network, as well as meet a number of dedicated scientists. I also had many insightful, thought-provoking discussions with other attendees. I believe we will be able to continue our discussions in future formal or informal collaborations. It was a great experience and I hope to attend more conferences in the future to present scientific findings.
The role of the epicardium in cardiac repair
The Anne McLaren Laboratory, Wellcome Trust –MRC Cambridge Stem Cell Institute, Forvie Site, University of Cambridge, Robinson Way, Cambridge CB2 0SZ, UK
Division of Cardiovascular Medicine, University of Cambridge, ACCI Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK
At present, around 25 Million people worldwide suffer from chronic heart failure. Following the exhaustion of medical and device therapy, these patients have no other therapeutic option to make up for the loss of contractile working myocardium other than heart transplantation. Approaches in regenerative medicine making use of human pluripotent stem cell (hPSC)-derived cardiomyocytes in order to remuscularise the infarcted heart and restore function have provided promising preclinical data in large animal models but limitations such as cardiomyocyte immaturity and poor vascularisation remain. Concomitantly, over the past decade the epicardium has sparked much interest in regenerative cardiovascular medicine due to its pivotal role in embryonic heart development, serving as a cellular source for coronary smooth muscle cells and interstitial fibroblasts. Here the role of hPSC-derived epicardial cells is discussed in the context of regenerative cardiovascular medicine.
It is in early embryonic heart development, that the epicardium displays unique functionality that makes it an interesting candidate for cardiac repair. At around 3.5 weeks of human heart development epicardial cells arise from the proepicardial organ and cover the surface of the embryonic heart tube. The epicardium then starts to undergo epithelial to mesenchymal transition (EMT) and invades the subepicardial space and subjacent compact myocardium . During this process epicardial cells give rise to smooth muscle cells (SMC), required for the formation of the coronary vasculature as well as to interstitial cardiac fibroblasts (CF), which result in cardiac compaction and maturation [2-4] (Figure 1, Panel A). Epicardial outgrowth inhibition in chicken embryos has resulted in malformation of the coronary vasculature and myocardial non-compaction, resulting in early embryonic death . The developmental cues driving the chemically defined differentiation of epicardial cells as well as epicardium-derived smooth muscle cells and fibroblasts from human pluripotent stem cells are shown in Figure 2. In this context, some of our own data have shown that the fate of epicardial cells is system and developmental stage dependent (Figure 1, Panel B). Using an athymic rat model of myocardial infarction, we observed that intramyocardial injection of hPSC-derived epicardial cells into the infarct zone resulted in robust fibroblast graft formation. In contrast, using a developmental chicken embryo transplantation of hPSC-epicardial cells into the extraembryonic vasculature resulted in formation of epicardium-derived smooth muscle cells and integration thereof into pre-existing chicken vasculature. Additionally, pioneering work by Nicola Smart and Paul Riley has shown that if primed with Thymosin beta 4, epicardial cells are even capable of giving rise to cardiomyocytes . Increasing the efficiency of this process could open up another avenue in epicardium-mediated cardiac repair.
The only therapeutic option for patients with heart failure that directly addresses the underlying loss of cardiomyocytes is heart transplantation. Despite a huge potentially eligible patient population only as many as 200 heart transplantations are performed in the entire UK every year. Regenerative medicine, using human pluripotent stem cells, including induced pluripotent stem cells (iPSC) or human embryonic stem cells (hESCs), is a promising novel therapeutic domain that has fostered the rise of 3D-engineered heart tissue (3D-EHT)-based approaches as well as those making use of direct intramyocardial cell injection of human pluripotent stem cell (hPSC)-derived cardiomyocytes. The latter of the two approaches has been very successful in rodent models of myocardial infarction where transplantation of hESC-derived cardiomyocytes has led to robust cardiovascular graft formation and rescue of global host heart function [7, 8]. Endeavours to translate this approach to a model that more closely resembles human disease demonstrated that transplantation of 1 Billion hESC-derived cardiomyocytes results in robust graft formation in infarcted non-human primates and more recently this was also shown for hiPSC-derived cardiomyocytes using the same model [9, 10]. While these studies have provided compelling pre-clinical data in a close-to-clinical-environment setting, elegantly using clinical grade heart catheters for percutaneous vascular access and delivery into the left ventricular wall, the field is eagerly awaiting functional data corroborating the concept that robust cardiac grafting also results in improvement of host heart function. While this technology has provided promising evidence for clinical applicability and translational potential a number of shortcomings remain.
Mechanistic insights into embryonic organ development have rendered possible the in vitro generation of a large number of different body tissues from hPSCs. While derived and terminally differentiated cells express all markers of their adult human counterparts and exhibit functionality, given the process and the time required for their derivation, they fall short of reaching sound levels of maturity. For cardiomyocytes, this means that hPSC-derived, beating monolayer cultures at best resemble the phenotype of those found in a third trimester embryo [11, 12]. Transplantation of cardiomyocytes with a relatively immature phenotype means suboptimal structural integrity of cardiac grafts and related function post engraftment. Additionally, cell death following transplantation into ischaemic myocardium is high resulting in optimizable cardiac graft size and vascular supply to grafts is poor compared to physiologic myocardial tissue . Meeting these shortcomings could potentially catalyse critical progress in regenerative cardiovascular repair. While the embryonic identity of hPSC-derived tissues is often seen as a drawback in regenerative medicine, the functionality displayed by the epicardium in early embryonic heart development and reflected by hPSC-derived epicardium could critically aid meeting some of the key limitations currently present in cardiac repair, including vascularisation and maturation.
Regenerative medicine has fostered the paradigm that a better understanding of developmental processes can aid organ regeneration. While only deeper molecular insights have allowed for the derivation of specific body tissues in vitro, the generation of more complex tissue-systems could help advance cardiac repair beyond current limitations. The use of the epicardium as an adjuvant cardiovascular therapeutic for tissue engineering application is hence a tantalising approach. HPSC-derived epicardial cells, if added to cardiomyocytes in 3D-EHTs could help to better vascularise transplantable heart patches and provide for structural integrity and maturation . On a different note the capability to generate epicardial cells will also allow for mimicking of developmental processes like embryonic heart tube formation. Such a multi-cellular construct, incorporating epicardium, myocardium and endocardium, if devised, would allow for unprecedented opportunities to move forward our understanding of cardiac developmental and regenerative processes. Furthermore, the field of drug toxicity testing could substantially benefit from more mature hiPSC-derived cardiomyocytes to gain a more high-fidelity readout of calcium traces that more closely resemble the toxic effects seen in patients following drug administration. The functionality of hPSC-derived epicardial cells seen in preclinical studies makes them a potentially interesting adjuvant therapeutic for cardiac repair that promises to address some of the key limitations that the field currently faces. This could usher in a new, more complex era of cardiac regeneration that will move closer to generating bona fide cardiac tissue and more efficient repair.
The 21st annual meeting of the Scottish Cardiovascular Forum (SCF) was held on the 3rd of February in Trinity Biomedical Sciences Institute, Trinity College Dublin. The SCF is a meeting focused on different aspects of cardiovascular research including vascular dysfunction, inflammation, oxidative stress, cardiac and vascular remodelling.
The beauty of the SCF is that it provides a platform for undergraduate students, PhD students and postdocs to present their research findings in a comfortable and encouraging environment alongside principal investigators and leaders in cardiovascular research. It enables open discussion among all participants and facilitates the exchange of new ideas, new connections and networking opportunities among basic science and translational cardiovascular researchers from Scotland, Ireland, Northern Ireland and England.
This year’s programme was delivered primarily by PhD students and postdocs of all stages and included plenary lectures presented by Dr. Mathew Campbell and Professor Mark Little (TCD). Dr Mathew Campbell (TCD), opened the meeting by discussing his work on the importance of the blood-brain barrier and the crucial role it plays especially in neurological conditions such as schizophrenia, traumatic brain injury and chronic traumatic encephalopathy. He highlighted the important role that the tight junction protein, claudin-5, plays in regulating the blood-brain barrier integrity. His research group found that targeted suppression of claudin 5 induced psychosis-like behaviour in an inducible claudin-5 knockdown mouse model with these mice displaying characteristic features of schizophrenia.
The Roger Wadsworth competition swiftly followed the keynote lecture from Dr. Campbell. This competition is named in memory of Roger M. Wadsworth, a Professor of Cardiovascular Pharmacology at Strathclyde University, who made huge contributions both scientifically and academically in the field of cardiovascular research where he is held in the highest esteem as a supervisor for his commitment and mentoring of young cardiovascular scientists. Final year PhD students must present their research and the award is given to the student who delivers the most outstanding oral presentation at the meeting along with their achievements during their PhD. This year’s topics covered a diverse range of topics including epigenetic therapy for heart failure; optical imaging for the detection of microcalcification in atherosclerotic plaques; and the role of protein phosphatase 2A in modulating permeability of the blood-brain barrier. Personally, it was an honour to be given the opportunity to present work from my PhD in the Roger Wadsworth competition. My research has demonstrated that administration of the DNA methylation inhibitor, 5-azacytidine, can reduce aberrant cardiac remodelling in the setting of hypertension-induced cardiac injury and improve cardiac function in the naturally aged heart. It is the hope that pharmacological manipulation of epigenetic mechanisms may potentially lead to novel therapeutic strategies for cardiomyopathies where remodelling plays an important role in driving disease with limited effective treatment options. This work was carried out as part of a commercialisation grant funded by Enterprise Ireland.
After a very exciting morning session, it was time for lunch and the conference poster session. All presenters did a fantastic job of conveying a broad range of topics and methodologies to the audience. It was very motivating to see the vast quantity and quality of research that is being carried out by research groups in Scotland, Ireland, Northern Ireland and England. Following lunch, the afternoon session covered a collection of different areas of cardiovascular research from the role of the anti-angiogenic protein FKBPL in cardiac dysfunction and preeclampsia to the role and therapeutic delivery of the counter regulatory renin-angiotensin system in stroke and cardiac hypertrophy.
The afternoon was rounded off with an intriguing talk from Professor Mark Little (TCD), presenting his work on the rare autoimmune disease Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Prof Little elaborated through a clinical case study of how there is large variability in the clinical onset observed in ANCA vasculitis. Due to the clinical variability of rare diseases such as ANCA vasculitis, Prof. Little highlighted the critical importance for establishing universal networks to bring together concerted efforts to improve patient care. He drew on recent advancements in the field including the development of a mobile based app for patients with vasculitis known as patientMpower which offers personalised tips on staying well and help with medication adherence and provides a cloud based platform to store clinical data. This will ultimately enhance patient-physician interaction and reduce the clinical variability of ANCA vasculitis as it allows the linkage of relapse events to environmental factors.
The meeting was brought to a close with the prize-giving ceremony delivered by Dr. Susan Currie. The standard of presentations by all competing had been excellent. Difficulty in selecting the winners of each category was a point which Dr. Currie emphasized in her closing speech. To say that I was shocked when my name was announced as the winner of the Roger Wadsworth prize was an understatement. The Roger Wadsworth prize was presented by Professor Wadsworths’ wife, Dr Moira Wadsworth. It was a true honour to receive this prestigious award from Moira and an absolute pleasure to meet her. Her kind words of congratulations were heart-warming and made the achievement that little bit more special.
The SCF Best Oral Presentation prize was awarded to Ms. Karla O’Neil of Queens University Belfast for her captivating talk on the regulatory role of NOX4 in cord-blood derived endothelial colony forming cells to promote post-ischaemic revascularisation. The final prize of the afternoon was the SCF Best Poster Presentation which was awarded to Ms. Eleanor Gill of Queen’s University Belfast for her poster titled “NOX4 NADPH oxidase is a key regulator of endothelial cell function in experimental diabetes. All abstracts of the presentations and posters will be published in the journal Heart, following a recent agreement that will allow the research showcased from this year’s SCF meeting to be shared with the wider scientific community.
I would now like to take the opportunity to thank both the SCF and the Wadsworth family for their continued support of young and driven cardiovascular researchers. Furthermore, I think I speak for everyone in thanking Professor Paul Spiers, Dr. Margaret Lucitt, Dr. Martina Hennessy and Ms. Gillian Casey for arranging such a fantastic event. It was thoroughly entertaining, enlightening, and I very much look forward to next years meeting. SCF2019 meeting will take place in the Scottish Highlands in Inverness, so keep your eyes peeled on www.scf.strath.ac.uk for updates! - Until next year!