Cardiovascular Research at the frontier of biomedical science

At a time when healthcare has been placed in the front of peoples’ minds by the novel coronavirus disease 2019 (COVID-19) outbreak, the importance of scientific discovery as a fundamental driving force for clinical delivery—an explicit mission of the Cardiovascular Research journal—has become a beacon of hope that many across the world now look to.1 One of the key venues for discussion of such advances in basic science within the cardiovascular field is the biennial conference Frontiers in CardioVascular Biomedicine (FCVB). Originally planned to take place in Budapest in 2020, it was recently announced to be postponed until 2021 as a result of the ensuing pandemic. While much of the original programme for FCVB 2020 will remain the same for the future conference, FCVB 2021, consisting of novel basic science developments in cardiac and vascular biology, this delay will also provide a key opportunity to discuss cardiovascular effects of COVID-19 as more data steadily become available.2 In this global and connected era, sharing current scientific literature and information is one of the most important foundations to building advances in basic and translational science, and clinical delivery. To that end, Cardiovascular Research has curated a virtual issue highlighting reviews and original research papers corresponding to the intended programme of the FCVB 2020 meeting that would have taken place this year.3,4 The virtual issue complemented the journal's popular online, virtual session entitled ‘How to publish your Cardiovascular Research’ that took place on Wednesday 29th April 2020 and attracted hundreds of clinicians and researchers alike across the world. With the postponement in mind, we believe it is even more important to bring the most recent scientific discoveries that were supposed to be presented at FCVB 2020 to the attention of our readers. To begin with, genetics remains a through line for understanding the basis of cardiovascular diseases to developing small molecule-based therapeutics. Indeed, this topic has been a leading focus of numerous abstracts submitted to FCVB. These topics are also regularly featured in Cardiovascular Research. Epigenetics is one of the most recurring themes in these studies. For example, maternal diet-induced obesity in mice was recently shown to promote cardiac dysfunction in the offspring.5 Such epigenetic mechanisms may also explain the effects of exercise, where, for example, in a mouse model of arrhythmogenic cardiomyopathy (ACM), exercise could restore dysregulated gene expression in cardiac myocytes and have therapeutic value in ACM.6 Non-coding RNAs and the transcriptome were additionally to feature heavily at FCVB. Heart failure continues to cast a long shadow on global public health, and microRNAs could be used to help stratify populations of heart failure patients with preserved ejection fracture (HFpEF).7 Similarly, microRNA-424(322) may be a useful diagnostic marker of progression of pulmonary arterial hypertension, potentially directly affecting heart function with a role in right ventricular hypertrophy.8 Beyond microRNAs, small nucleolar RNAs (snoRNAs) such as 14q32 snoRNAs, encoded by the same locus as microRNAs suspected to be involved in vascular remodelling and cardiovascular disease, have now been proposed to have an independent role in cardiovascular pathophysiology.9 Another example of the far-reaching influence of non-coding RNAs in cardiac pathologies, recently published in Cardiovascular Research, compared human cardiac long non-coding RNA (lncRNA) profiles in controls and patients with dilated cardiomyopathy (DCM) and hinted at the diverse functional roles of these molecules in different heart cell types.10 Furthermore, it has emerged that the lncRNA TUG1, already implicated in atherosclerosis, may have additional functions in regulating osteogenic differentiation in calcific aortic valve disease.11 With therapeutics in mind, a recently characterized lncRNA splice variant of the AZIN2 gene was shown to be up-regulated in adult hearts and to suppress endogenous cardiac regeneration.12 All of these discoveries add extra weapons to the armoury of cardiac repair.13,14 One of the main obstacles in these approaches include the low engraftment and survival rate of transplanted cells, and how to overcome these is discussed extensively in a European Society of Cardiology (ESC) Position Paper on novel tissue engineering strategies.15 Another hot topic requiring mechanistic dissection is sex-specific differences in cardiovascular disease, and this has become a priority in cardiovascular research with increased focus and emerging data.16–18 It is therefore unsurprising that this was to feature prominently within the FCVB programme. Mechanisms based on microRNAs and epigenetics as discussed earlier may underlie the differential pathophysiology of cardiovascular disease in women, and help explain the increased prevalence of certain cardiovascular diseases, such as HFpEF, in women.19 For example, one such mechanism could be linked to the protective effects of ovarian hormones in mice. Disruption of the circadian rhythm resulting in the development of age-dependent cardiomyopathy may be prevented by ovarian hormones, hinting at the contribution of biological sex to cardiac remodelling, renewal, and growth.20 A topic prominent in studies submitted for presentation at FCVB is that of the cardiotoxic effects of various drugs, particularly in cancer treatments. For example, immune checkpoint inhibitors, though promising for several cancer types, can cause cardiovascular toxicities such as non-inflammatory heart failure, myocarditis, and pericardial disease.21–23 New understanding brought to the forefront of cardioprotection includes the role of the innate immune system in the acute response to ischaemia–reperfusion injury and how this can be manipulated to protect the heart and coronary circulation.24,25 Furthermore, trials into cell therapies following acute myocardial infarction have shown that exosomes secreted by cardiac-resident progenitor cells may be more cardioprotective than those from bone marrow-derived mesenchymal progenitor stem cells.26 Indeed, extracellular vesicles have their own dedicated FCVB session—owing to the increasing number of such publications. These are expertly summarized by the ESC Working Group on Cellular Biology of the Heart Position Paper.27 Protecting the heart and addressing cardiotoxicities has become one of the bustling frontiers of basic cardiovascular research.28–30 For more on Cardio-oncology and Cardioprotection, Cardiovascular Research has published two Spotlight Issues highlighting advances and current knowledge in these flourishing areas.28,31 A look at the innate immunity and its role in ischaemia–reperfusion injury as a possible target for acute cardioprotection.24 Atherosclerosis, as the culprit of numerous cardiovascular pathologies including various ischaemic episodes, was to be discussed more extensively from a translational perspective during this year’s FCVB. As early stages of atherosclerotic disease are characterized by infiltration of myeloid cells, novel methods have been applied recently to identify and map specific myeloid subsets at play within the atherosclerotic aortas of mice.32 Other tracking techniques have been utilized to determine the origin and fate of smooth muscle cells in atherosclerosis, providing new insights into current models of this prevalent disease.33 Cardiovascular research has also expanded the use of approaches widely used by neuroscience, such as optogenetics. Recently, genetically modified, light-sensitive ion channels have been utilized as a means of terminating atrial tachyarrhythmia in mice.34 Indeed, electrophysiology-oriented research has brought substantial discoveries in recent years. This includes knowledge of the differential regulation of neuronal sodium channels in the failing human myocardium, and an enhanced understanding of G protein-coupled receptors in the heart using designer receptors solely activated by designer drugs (DREADD) technology.35,36 One perhaps historically under-recognized aspect of cardiovascular biology is the effects of the coronary microvasculature, implicated in ischaemic heart disease. In March 2020, this burgeoning and fascinating topic was thoroughly explored in a Cardiovascular Research Spotlight Issue on Coronary microvascular dysfunction: examining the basic, translational, and clinical aspects of this emerging area.37 One of the intended focuses at FCVB 2020 was to give attendees the opportunity to examine how the microcirculation presents a window into cardiovascular risk, and how comorbidities can play a role in coronary microvascular dysfunction.38 This adds to the repertoire of key symposia which were to take place at the meeting, which also include the role of the autonomic nervous system in coronary pathophysiology, mechanics, and vascular disease, and inflammation and immunity in the heart.39–41 As mentioned, to help bridge the gap between the absence of this year’s FCVB and to herald FCVB 2021 in Budapest next year, our curated virtual issue from Cardiovascular Research explores some of the recent highlight papers relevant to the original FCVB programme. Additionally, in our special online session entitled ‘How to publish your Cardiovascular Research’, we shared insights on how to publish high-impact science which was followed by talks discussing visibility for authors who publish in Cardiovascular Research, ethics in scientific publishing, as well as authors of top papers discussing their highly cited papers and most recent work.42 We also encourage authors, including Young Investigator Award finalists, to submit their work to Cardiovascular Research, as we continue to remain dedicated to helping drive the development of the cardiovascular science community at the frontiers, as well as actively promoting and supporting young investigators. We anticipate and look forward to a fruitful FCVB conference in Budapest, 2021 and hope to see you all there.2 Biography: Sarah K. Brown is Assistant Editor of Cardiovascular Research and has degrees in both Pharmacology (BSc) and Cardiovascular Sciences [MSc (Med Sci)] from the University of Glasgow, UK. She is based in the Editorial Office of the Journal, within the Institute of Cardiovascular and Medical Sciences at the University of Glasgow. Biography: Adam M. Sheikh is part of the Editorial Team at Cardiovascular Research, responsible for helping to manage the Onlife section of the journal. He has degrees in Genetics (BSc) and Biomedical Sciences (MRes) from the University of Glasgow (UK), where he is currently undertaking his medical studies. Biography: Professor Tomasz J. Guzik is the current Editor-in-Chief of Cardiovascular Research. He is the Regius Professor of Physiology and Cardiovascular Pathobiology and an Honorary Consultant Physician in Cardiology at the University of Glasgow. He also serves as a Professor of Medicine at Jagiellonian University Collegium Medicum in Krakow, Poland. Notable recognitions include the honorary Bernard and Joan Marshall Prize in Research Excellence from the BSCR and the prestigious Corcoran Award Lecture at the American Heart Association. He is a recipient of a European Research Council Grant. Professor Guzik research focuses on vascular biology, hypertension, and clinical immunology.