Endothelial cell functions are critical for cardiovascular health, and endothelial cell dysfunction underlies the pathology of many cardiovascular diseases. This review summarises the major aspects of endothelial physiology, which together contribute importantly to vascular homeostasis. These include regulation of haemostasis and thrombosis, vascular tone and permeability, lipid transport into the vessel wall, and leukocyte traffic from blood to tissue. Key examples are presented illustrating where endothelial cell dysfunction drives pathology and disease. Signalling pathways that are targets for current or future drug treatments for cardiovascular disease are highlighted. Control of endothelial cell phenotype is described in relation to vasculogenesis, angiogenesis, and other aspects of endothelial cell plasticity. This provides an overall framework linking endothelial physiology and pathology. By virtue of its pan-organ localisation endothelial phenotype is differentiated in multiple ways between different vascular beds due to its responses to organ-specific stimuli, which can change in disease. By virtue of its exposure to blood, endothelial phenotype is further maintained or modulated by prevailing and changing physical and chemical signals.

The British Heart Foundation's (BHF) annual statistical compendium is a comprehensive source of accessible epidemiological data in relation to cardiovascular disease (CVD) in the UK. Using datasets with multiple years of data from the compendium we have analysed trends in mortality, morbidity, and treatment for CVD within the UK. CVD mortality in the UK has consistently declined over recent decades, from 1045 deaths per 100 000 in 1969, shortly after the BHF was founded, to 255 per 100 000 in 2019. Despite this remarkable improvement, inequalities in CVD mortality persist in the UK nations, for example in 2019 the death rate in Scotland was 326 deaths per 100 000 compared with 246 per 100 000 in England. Improvements in CVD mortality have been paralleled by increased use of primary prevention medications (anti-hypertensives and statins) and interventional procedures. In recent years, progress in mortality outcomes has stalled, probably due to a combination of factors including a rise in risk factors such as obesity and diabetes. In terms of morbidity, CVD remains a significant burden in the UK, accounting for at least 1.18 million hospital admissions and reflects the enormous economic burden of CVD, estimated at 19bn pound in the UK. Our results highlight the importance of accessible and comprehensive statistics in relation to the burden of CVD and the value of the BHF's annual compendium in drawing out conclusions and opportunities for future research. One key area is to improve the data on which estimation of prevalence is based. There is also a need for ongoing work to better understand the root causes of disparity between socio-economic groups in relation to CVD. One important way to address this will be to improve the consistency of reporting of CVD health data across all nations of the UK. Understanding the causes will inform UK healthcare planning in addition to providing analytical insights that will be applicable in other countries.

Extra-column band dispersion during the transport of a sample band from the injector to the column can be reduced by a flow rate program starting with a low flow rate until the sample band has approached to, or just entered into the column, followed by an increased flow rate suitable for the solute separation in the column. Such a sample introduction method increased the plate counts of a 50 mm long column, 1.0 or 2.1 mmID, especially for early-eluting solutes by up to several times compared to a conventional elution method, when a 0.254 mmID, 15.2 cm connection tubing was used. Increase in plate counts of up to 50–70% was possible for solutes with retention factors smaller than 1.0 for the columns connected with a 0.13 mmID, 15 cm tube. The method also seems to reduce the contribution of the void space at the column inlet to the band dispersion. The elution method including a slow transport of the sample band in the pre-column space of 10 μL or less may require a little longer separation time than normal elution, but it was shown to be effective for increasing the observed efficiency of a small column for solutes with small retention factors.

Tomasz Guzik: Welcome. As a part of our Cardiovascular Research Onlife interview series for this special European Society of Cardiology (ESC) edition, we have the honour of speaking to the outgoing chair of the Council on Basic Cardiovascular Science (CBCS), Professor Jeremy Pearson, and the incoming chair, Professor Johannes Waltenberger, to talk to us about the present and the future of basic science in cardiovascular research in the ESC. Thank you both very much for joining us. Jeremy Pearson: Thank you. The Council on Basic Cardiovascular Science was founded originally after discussions in 2003 at the ESC between basic scientists who were interested in trying to grow the profile of basic science at the main ESC congress—which at that time was very small. We realized that underpinning basic science is vital for the translation into modern medicine and clinical practice. We felt that the ESC should be enabled to recognize this better by founding a council. There were discussions with the board of the ESC and in Biography: Jeremy Pearson is Emeritus Professor of Vascular Biology at King’s College London, in addition to being Associate Medical Director of the British Heart Foundation. Professor Pearson is the outgoing chair of the CBCS. Biography: Johannes Waltenberger is Professor and Chair of Internal Medicine, Cardiology and Vascular Medicine at University of Münster. Professor Waltenberger is the incoming chair of the Council on Basic Cardiovascular Science (CBCS).

This editorial refers to ‘Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress’ by J.-R. Moonen et al. , doi:10.1093/cvr/cvv175. In most healthy blood vessels, average endothelial cell turnover is very low, with cell lifespan estimates of up to many years—hardly indicative of a cell type that might be expected to undergo substantial proliferative and phenotypic changes in response to external stimuli. This contrasts with the relatively rapid and continuous turnover of many epithelial cell linings, with replacement by generation from local progenitor cells, such as in the skin or gut. However, this perspective needs to be balanced by our knowledge of significant and rapid alterations in endothelial cell behaviour in the control of vascular homeostasis, for example in response to altered shear stress or to pro-inflammatory mediators. And, indeed, there are also clear examples of the ability of adult endothelium to chronically adapt its phenotype. One of these is the generation of so-called high endothelial venules at sites of chronic inflammation, where the thickened endothelial cells are specialized to enhance lymphocyte trafficking and the phenotype …

Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44 mg protein/L) concentration-dependently induced upregulation of vasoconstrictive ETB receptor expression with increase in the receptor-mediated vasoconstriction, elevated levels of the ETB receptor mRNA and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126) or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced upregulation of vasoconstrictive ETB receptor expression. Actinomycin D (general transcriptional inhibitor) almost completely inhibited the LDL effects. In conclusion, LDL induces upregulation of vasoconstrictive ETB receptor expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent transcriptional mechanisms.

Background: Scleroderma (SSc) is a complex autoimmune disorder that can be characterised by the presence 2of circulating autoantibodies to nuclear, cytoplasmic and cell surface antigens. In particular antibodies directed against endothelial cell antigens (anti-endothelial cell antibodies; AECA) have been detected.ICAM-1 is an adhesion molecule expressed on the surface of human endothelial cells. We have previously shown that cross-linking ICAM-1 with monoclonal antibodies leads to pro-inflammatory activation of human endothelial and vascular smooth muscle cells and that cardiac transplant recipients with transplant associated vasculopathy make antibodies directed against ICAM-1.Objectives: To determine whether SSc patients make antibodies directed against ICAM-1 and whether these antibodies induce pro-inflammatory activation of human endothelial cells in vitro.Methods: Using recombinant ICAM-1 as capture antigen, an ELISA was developed to measure ICAM-1 antibodies in sera from SSc patients. Antibodies were purified using ICAM-1 micro-affinity columns. HUVEC were incubated with purified anti-ICAM-1 antibodies and generation of reactive oxygen species, and expression of VCAM-1 was measured.Results: Significantly elevated levels of anti-ICAM-1 antibodies were detected in patients with diffuse (dSSc; 10/31 32%) or limited (ISSc; 14/36 39%) scleroderma. Cross-linking of HUVEC with purified anti-ICAM-1 antibodies caused a significant increase in ROS production (2.471 +/- 0.408 fold increase above untreated after 150 min p < 0.001), and significant increase in VCAM-1 expression (10.6 +/- 1.77% vs 4.12 +/- 1.33%, p < 0.01).Conclusion: AECA from SSc patients target specific endothelial antigens including ICAM-1, and cause pro-inflammatory activation of human endothelial cells, suggesting that they are not only a marker of disease but that they contribute to its progression. (c) 2013 Elsevier Inc. All rights reserved.

Reviewed by: Collections in Context: The Organization of Knowledge and Community in Europe Jeremy D. Pearson Collections in Context: The Organization of Knowledge and Community in Europe, ed. Karen Fresco and Anne D. Hedeman (Columbus: The Ohio State University Press 2011) 340 pp. In the introduction to Collections in Context: The Organization of Knowledge and Community in Europe, Charlotte Bauer argues that for too long the term collection has been very narrowly defined. A true collection has traditionally been considered a singular act of authorship conceived by a collector, who then, with great intentionality, gathers, edits, and arranges the objects in question in order to tell a specific story or create a particular experience. Pre-modern collections seem to lack this authorial voice, being a hodge-podge of inheritances and gifts, rather than a thing intelligently designed. For this work’s contributors, however, this narrow definition has led scholars to neglect important medieval and early-modern collections that do not seem to fit it. The fourteen essays in Collections in Context, by contrast, challenge these assumptions, seeking to redefine “the collection” in the broadest of terms, an effort which allows for a reevaluation of medieval collections which, by the narrow definition, would qualify as mere miscellanies, despite the fact that they were systematically designed, deeply meaningful to their users, and capable of conveying potent and sophisticated messages. Through an analysis of various fourteenth to seventeenth century collections, these scholars assert that the real flaw is in our definition of the collection, rather than in the refusal of these particular collections to conform. In one way or another, the fourteen essays of Collections in Context reveal intentionality and purpose in collections that, at first glance, seem to have none. The essays are grouped into three parts, and those in part I begin by considering how collections are composed, ordered, and circulated. Peter Ainsworth, for example, suggests that e-Science tools will soon allow medieval and early-modern scholars to access, assemble and display high resolution images drawn from a wide and ever-expanding database. This technology will, in effect, create the potential for collections that are elastic and dynamic, constantly permuting as scholars tinker and adjust them to respond to ever-changing needs. The narrow definition of the static collection, permanently fixed in place and time, will, in other words, soon be rendered obsolete. The collections created by this new technology, however, will still require signifiers that connect their contents, and in her essay Nancy Freeman Regalado explores these very “dynamics of reading in a collection,” how iconographic motifs could be used by the makers and readers of manuscripts to bridge the contents within them (30). Specifically, she traces the motif of a winged knight that appears throughout MS Douce 308, and suggests that the motif encouraged a sophisticated and integrated reading of its texts, one that simultaneously emphasized the pursuit of worldly chivalric glory alongside the potentially competing ideal of preparing one’s soul for an impending apocalyptic struggle. Similarly, Marcus Keller examines the Thesoro politico, a collection of seemingly unrelated political essays and state reports, and identifies a common thread between them: the [End Page 174] Ottoman Empire. The editor of the Thesoro selected texts that treated the Turkish threat in different and sometimes contradictory ways, a deliberate incongruity that “reveals the anthological as an intrinsically political mode” (87). In part II, Anne D. Hedeman, Andrew Taylor, Craig Taylor, and Karen Fresco each consider how collections reveal invisible networks of texts, book producers, and readers through four case studies of the Shrewsbury Book (BL MS Royal 15 E. vi). This collection of epics, romances, and political treatises shows the ways cross-textual visual imagery, grounded in contemporary literary culture, could be used by book producers to make bold dynastic claims for their royal patrons, and texts could be carefully tailored to readers like Edward of Westminster, prince of Wales, to encourage not only a martial outlook but the actions to go with it. Finally, in part III, the remaining contributors focus on the ways collections build communities, with special attention devoted to innovative and non-traditional collections. Indeed, Erin K. Donovan describes the library of Louis de Bruges, a...