Cardiomyocyte-specific deletion of Sirt1 gene sensitizes myocardium to ischaemia and reperfusion injury
ConclusionsCardiac SIRT1 mediates AMPK activationvia LKB1 deacetylation, and AMPK modulates SIRT1 activityvia regulation of NAD+ level during ischaemia. SIRT1 and AMPK agonists have therapeutic potential for treatment of aging-related ischemic heart disease. (Source: Cardiovascular Research)
Source: Cardiovascular Research - February 2, 2018 Category: Cardiology Source Type: research

Novel concepts for the role of smooth muscle cells in vascular disease: towards a new smooth muscle cell classification
(Source: Cardiovascular Research)
Source: Cardiovascular Research - February 2, 2018 Category: Cardiology Source Type: research

Stretch-induced compliance: a novel adaptive biological mechanism following acute cardiac load
ConclusionsWe describe and translate to human physiology a novel adaptive mechanism, partly mediated by titin phosphorylation through cGMP –PKG signalling, whereby myocardial compliance increases in response to acute stretching. This mechanism may not function in the hypertrophic heart. (Source: Cardiovascular Research)
Source: Cardiovascular Research - February 1, 2018 Category: Cardiology Source Type: research

Vascular smooth muscle contraction in hypertension
AbstractHypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia, and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex-interacting systems such as the renin-angiotensin-aldosterone system, sympathetic nervous system, immune activation, and oxidative stress, which influence vascular smooth musc...
Source: Cardiovascular Research - January 31, 2018 Category: Cardiology Source Type: research

Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension
We present evidence for time- and location-specific changes in SMC proliferation in various animal models of PH; we highlight the transient nature (rather than continuous) of SMC proliferation, emphasizing that the heterogenic SMC populations that reside in different locations along the pulmonary vascular tree exhibit distinct responses to the stresses associated with the development of PH. We also consider that cells that have often been termed ‘SMCs’ may arise from many origins, including endothelia l cells, fibroblasts and resident or circulating progenitors, and thus may contribute via distinct signalling p...
Source: Cardiovascular Research - January 27, 2018 Category: Cardiology Source Type: research

Smooth muscle cell fate and plasticity in atherosclerosis
AbstractCurrent knowledge suggests that intimal smooth muscle cells (SMCs) in native atherosclerotic plaque derive mainly from the medial arterial layer. During this process, SMCs undergo complex structural and functional changes giving rise to a broad spectrum of phenotypes. Classically, intimal SMCs are described as dedifferentiated/synthetic SMCs, a phenotype characterized by reduced expression of contractile proteins. Intimal SMCs are considered to have a beneficial role by contributing to the fibrous cap and thereby stabilizing atherosclerotic plaque. However, intimal SMCs can lose their properties to such an extent t...
Source: Cardiovascular Research - January 27, 2018 Category: Cardiology Source Type: research

New models to study vascular mural cell embryonic origin: implications in vascular diseases
AbstractA key question in vascular biology is how the diversity of origin of vascular mural cells, namely smooth muscle cells (SMCs) and pericytes influences vessel properties, in particular the regional propensity to vascular diseases. This review therefore first describes the role and regulation of mural cells during vascular formation, with a focus on embryonic origin. We then consider the evidence that connects heterogeneities in SMC and pericyte origins with disease. Since this idea has major implications for understanding and modelling human disease, then there is a pressing need for new model systems to investigate ...
Source: Cardiovascular Research - January 27, 2018 Category: Cardiology Source Type: research

Integrated transcriptomic and regulatory network analyses identify microRNA-200c as a novel repressor of human pluripotent stem cell-derived cardiomyocyte differentiation and maturation
ConclusionsOur analyses demonstrate that miR-200c represses hESC-CM differentiation and maturation. The integrative computation and experimental approaches described here, when applied more broadly, will enhance our understanding of the interplays between miRNAs and TFs in controlling cardiac development and disease processes. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 24, 2018 Category: Cardiology Source Type: research

Role of smooth muscle cells in coronary artery bypass grafting failure
AbstractAtherosclerosis is the underlying pathology of many cardiovascular diseases. The formation and rupture of atherosclerotic plaques in the coronary arteries results in angina and myocardial infarction. Venous coronary artery bypass grafts are designed to reduce the consequences of atherosclerosis in the coronary arteries by diverting blood flow around the atherosclerotic plaques. However, vein grafts suffer a high failure rate due to intimal thickening that occurs as a result of vascular cell injury and activation and can act as ‘a soil’ for subsequent atherosclerotic plaque formation. A clinically-proven...
Source: Cardiovascular Research - January 24, 2018 Category: Cardiology Source Type: research

CETP inhibition and HDL: what is the trial REVEALing?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - January 24, 2018 Category: Cardiology Source Type: research

Niels Voigt talks to W. Jonathan Lederer, keynote lecturer at the “Göttingen Channels” Symposium 2017
Prof. Lederer discusses his scientific career as a pioneer in the field of cellular of calcium signalling and offers his wisdom to young researchers following his keynote lecture at the G öttingen Channels Symposium 2017 of the German Cardiac Society’s working group on cellular electrophysiology (AG 18). (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 24, 2018 Category: Cardiology Source Type: research

DARC matter(s) for inflammatory cells
(Source: Cardiovascular Research)
Source: Cardiovascular Research - January 24, 2018 Category: Cardiology Source Type: research

Sodium –hydrogen exchange inhibition attenuates glycoside-induced hypertrophy in rat ventricular myocytes
[Cardiovasc Res 2010;85(1):79 –89] (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 24, 2018 Category: Cardiology Source Type: research

Endogenous Sonic Hedgehog limits inflammation and angiogenesis in the ischaemic skeletal muscle of mice
ConclusionAlthough ectopic administration of Shh has previously been shown to promote ischaemia-induced angiogenesis, the present study reveals that endogenous Shh does not promote ischaemia-induced angiogenesis. On the contrary, the absence of Shh leads to aberrant ischaemic tissue inflammation and a transiently increased angiogenesis. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 22, 2018 Category: Cardiology Source Type: research

Identification of cardiac long non-coding RNA profile in human dilated cardiomyopathy
ConclusionsThis study provides a comparison of human cardiac lncRNA profiles in control and DCM. It illustrates the function and complex roles of the differentially expressed lncRNAs in different cell types in the heart, which may lead to new insights into the mechanisms and treatment strategies for DCM in the future. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 22, 2018 Category: Cardiology Source Type: research

Stat5-dependent cardioprotection in late remote ischaemia preconditioning
AbstractAimsTo study the protective effects of late remote ischaemic preconditioning (RIPC) against myocardial ischaemia/reperfusion (I/R) injury and determine whether Stat5 is involved in this protection by using cardiomyocyte-specific Stat5 knockout mice (Stat5-cKO).Methods and resultsMice were exposed to lower limb RIPC or sham ischaemia. After 24 h, the left anterior descending artery (LAD) was ligated for 30 min, then reperfused for 180 min. The myocardial infarct size (IS), apoptotic rate of cardiomyocytes, and serum myocardial enzymes were measured to evaluate for cardioprotective effects. Heart tissues were harvest...
Source: Cardiovascular Research - January 22, 2018 Category: Cardiology Source Type: research

Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock
ConclusionWe reported that TREM-1 is expressed and inducible in endothelial cells and plays a direct role in vascular inflammation and dysfunction. The targeted deletion of endothelialTrem-1 conferred protection during septic shock in modulating inflammatory cells mobilization and activation, restoring vasoreactivity, and improving survival. The effect of TREM-1 on vascular tone, while impressive, deserves further investigations including the design of endothelium-specific TREM-1 inhibitors. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 19, 2018 Category: Cardiology Source Type: research

Loss of KCNK3 is a hallmark of RV hypertrophy/dysfunction associated with pulmonary hypertension
ConclusionOur data indicate that loss of KCNK3 function and expression is a hallmark of the RV hypertrophy/dysfunction associated with PH. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 19, 2018 Category: Cardiology Source Type: research

Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKII δ expression in the aged atrium
ConclusionJNK2 activation up-regulates CaMKII δ expression in the aged atrium. This JNK2 regulation in CaMKIIδ expression occurs at the transcription level through the JNK downstream transcription factor c-jun. The discovery of this novel molecular mechanism of JNK2-regulated CaMKII expression sheds new light on possible anti-arrhythmia drug development. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 19, 2018 Category: Cardiology Source Type: research

IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis
ConclusionsIL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 19, 2018 Category: Cardiology Source Type: research

Elevated plasma catecholamines functionally compensate for the reduced myogenic tone in smooth muscle STIM1 knockout mice but with deleterious cardiac effects
ConclusionsSTIM1 deletion in smooth muscle results in attenuated myogenic tone and cytoskeletal defects with detrimental effects on the mechanical properties of arterial tissue. Although BP is maintained by elevated circulating catecholamine, this compensatory stimulation has a deleterious long-term effect on the myocardium. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 19, 2018 Category: Cardiology Source Type: research

Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis
AbstractIn the present review, we describe the causes and consequences of loss of vascular smooth muscle cells (VSMCs) or their function in advanced atherosclerotic plaques and discuss possible mechanisms such as cell death or senescence, and induction of autophagy to promote cell survival. We also highlight the potential use of pharmacological modulators of these processes to limit plaque progression and/or improve plaque stability. VSMCs play a pivotal role in atherogenesis. Loss of VSMCs via initiation of cell death leads to fibrous cap thinning and promotes necrotic core formation and calcification. VSMC apoptosis is i...
Source: Cardiovascular Research - January 18, 2018 Category: Cardiology Source Type: research

From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta
AbstractVascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissections share numerous characteristics, including aetiologies and histopathological alterations: vSMC disappearance, medial areas of mucoid degeneration, and extracellular matrix (ECM) breakdown. Three aetiologies predominate in TAAD in humans: (i) genetic causes in heritable familial forms, (ii) an associa...
Source: Cardiovascular Research - January 17, 2018 Category: Cardiology Source Type: research

Electrical coupling between cardiomyocytes and fibroblasts: experimental testing of a challenging and important concept
This editorial refers to ‘Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart’ by M. Rubartet al., pp. 389 –400. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 17, 2018 Category: Cardiology Source Type: research

Smooth muscle cells of intracranial vessels: from development to disease
AbstractCerebrovascular diseases that cause ischaemic or haemorrhagic stroke with subsequent loss of life or functional capacity due to damage of the brain tissue are among the leading causes of human suffering and economic burden inflicted by diseases in the developed world. Diseases affecting intracranial vessels are significant contributors to ischaemic and haemorrhagic strokes. Brain arteriovenous malformations, which are a collection of abnormal blood vessels connecting arteries to veins, are the most common cause of intracranial haemorrhage in children and young adults. Saccular intracranial aneurysms, which are path...
Source: Cardiovascular Research - January 16, 2018 Category: Cardiology Source Type: research

Deoxycorticosterone acetate-salt hypertension activates placental growth factor in the spleen to couple sympathetic drive and immune system activation
ConclusionOverall, our study demonstrates that DOCA-salt requires an intact sympathetic drive to the spleen for priming of immunity and consequent BP increase. The coupling of nervous system and immune cells activation in the splenic marginal zone is established through a sympathetic-mediated PlGF release, suggesting that this pathway could be a valid therapeutic target for hypertension. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 8, 2018 Category: Cardiology Source Type: research

Cardiovascular protection by Nox4
This editorial refers to ‘Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling’ by M. Zhanget al., pp. 401 –408. (Source: Cardiovascular Research)
Source: Cardiovascular Research - January 8, 2018 Category: Cardiology Source Type: research

Endothelial –mesenchymal transition in atherosclerosis
AbstractAtherosclerosis is an inflammatory disease resulting in the hardening and thickening of the wall of arteries and the formation of plaques, which comprise immune cells, mesenchymal cells, lipids, and extracellular matrix. The source of mesenchymal cells in the atherosclerotic plaques has been under scrutiny for years. Current endothelial-lineage tracing studies indicate that the endothelium is a source for plaque-associated mesenchymal cells. Endothelial cells can acquire a mesenchymal phenotype through endothelial –mesenchymal transition (EndMT), wherein the expression of endothelial markers and functions is ...
Source: Cardiovascular Research - January 4, 2018 Category: Cardiology Source Type: research

Non-coding RNAs: key regulators of smooth muscle cell fate in vascular disease
AbstractThe vascular smooth muscle cell (SMC) is one of the most plastic cells in the body. Understanding how non-coding RNAs (ncRNAs) regulate SMC cell-fate decision making in the vasculature has significantly enhanced our understanding of disease development, and opened up exciting new avenues for potential therapeutic applications. Recent studies on SMC physiology have in addition challenged our traditional view on their role and contribution to vascular disease, mainly in the setting of atherosclerosis as well as aneurysm disease, and restenosis after angioplasties. The impact of SMC behaviour on vascular disease is no...
Source: Cardiovascular Research - December 29, 2017 Category: Cardiology Source Type: research

The evolution of Cardiovascular Research Onlife: online and on demand
The new editor-in-chief and editorial team are delighted to continue the fruitful partnership with the European Society of Cardiology (ESC) Scientists of Tomorrow to further evolve theCardiovascular Research online platform, Onlife. Onlife was established in April 2017 with the aim of bringing together commentaries and opinions from both young scientists and world-leading principal investigators in basic and clinical research for the mutual benefit of both fields. Since then, Onlife has become a popular feature of the journal, with its material downloaded 5277 times since its launch. Onlife has been a very successful initi...
Source: Cardiovascular Research - December 25, 2017 Category: Cardiology Source Type: research

From clinical observations to molecular mechanisms and back to patients: the successful circuit of the CANTOS study
(Source: Cardiovascular Research)
Source: Cardiovascular Research - December 25, 2017 Category: Cardiology Source Type: research

Professor Charalambos Antoniades interviews Professor Tomasz Guzik, incoming Editor-in-Chief of Cardiovascular Research
(Source: Cardiovascular Research)
Source: Cardiovascular Research - December 25, 2017 Category: Cardiology Source Type: research

Ketone bodies to the rescue for an aging heart?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - December 25, 2017 Category: Cardiology Source Type: research

Cardiovascular Research: new challenges and new horizons
I am honoured and delighted to be taking over the helm ofCardiovascular Research, as the Editor-in-Chief, from Professor Karin Sipido. It is a huge honour, asCardiovascular Research, brought to its excellence by previous Editors-in-Chief, is one of the strongest journals in basic and translational cardiovascular sciences worldwide. It is also one of the European Society of Cardiology ’s (ESC) most important assets, supporting the overall mission of the Society. It will be exciting to lead the journal into a new phase of its growth, after 50 years of service to the cardiovascular community. The journal was init...
Source: Cardiovascular Research - December 25, 2017 Category: Cardiology Source Type: research

IL-17 in atherosclerosis: the good and the bad
(Source: Cardiovascular Research)
Source: Cardiovascular Research - December 25, 2017 Category: Cardiology Source Type: research

Optogenetic termination of atrial fibrillation in mice
ConclusionWe provide the first evidence for optogenetic termination of atrial tachyarrhythmia in intact hearts from transgenic as well as wild type miceex andin vivo. Thus, this report could lay the foundation for the development of implantable devices for pain-free termination of AF. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 23, 2017 Category: Cardiology Source Type: research

Lineage tracking of origin and fate of smooth muscle cells in atherosclerosis
AbstractAdvances in lineage-tracking techniques have provided new insights into the origins and fates of smooth muscle cells (SMCs) in atherosclerosis. Yet new tools present new challenges for data interpretation that require careful consideration of the strengths and weaknesses of the methods employed. At the same time, discoveries in other fields have introduced new perspectives on longstanding questions about steps in atherogenesis that remain poorly understood. In this article, we address both the challenges and opportunities for a better understanding of the mechanisms by which cells appearing as or deriving from SMCs...
Source: Cardiovascular Research - December 23, 2017 Category: Cardiology Source Type: research

Exploring immune checkpoints as potential therapeutic targets in atherosclerosis
AbstractIn the past decades, the inflammatory nature of atherosclerosis has been well-recognized and despite the development of therapeutic strategies targeted at its classical risk factors such as dyslipidemia and hypertension, atherosclerosis remains a major cause of morbidity and mortality. Additional strategies targeting the chronic inflammatory pathways underlying the development of atherosclerosis are therefore required. Interactions between different immune cells result in the secretion of inflammatory mediators, such as cytokines and chemokines, and fuel atherogenesis. Immune checkpoint proteins have a critical rol...
Source: Cardiovascular Research - December 22, 2017 Category: Cardiology Source Type: research

LUMA in cardiac development and function
This editorial refers to ‘Luma is not essential for murine cardiac development and function' by M.J. Stroudet al., pp. 378 –388. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 21, 2017 Category: Cardiology Source Type: research

Anthracycline cardiotoxicity: the importance of horizontally integrating pre-clinical and clinical research
This editorial refers to ‘Diverging effects of enalapril or eplerenone in primary prevention against doxorubicin-induced cardiotoxicity’ by R. Hullinet al., pp. 272 –281 and ‘Inhibition of the cardiac myocyte mineralocorticoid receptor ameliorates doxorubicin-induced cardiotoxicity’ by A. Lotheret al., pp.282 –290. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 19, 2017 Category: Cardiology Source Type: research

Normal interventricular differences in tissue architecture underlie right ventricular susceptibility to conduction abnormalities in a mouse model of Brugada syndrome
ConclusionsNormal structural heterogeneities present in the RV are responsible for increased vulnerability to conduction slowing in the presence of reduced sodium channel function. Heterogeneous conduction slowing seen in the RV will predispose to functional block and the initiation of re-entrant ventricular arrhythmias. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 18, 2017 Category: Cardiology Source Type: research

Mitochondrial targeted peptides preserve mitochondrial organization and decrease reversible myocardial changes in early swine metabolic syndrome
ConclusionsDisorganization of cardiomyocyte cytoskeletal-mitochondria-SR network is associated with cardiac reversible changes in early MetS, preceding overt cardiac dysfunction. These findings may introduce novel therapeutic targets for blunting cardiac damage in early MetS. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 18, 2017 Category: Cardiology Source Type: research

An autofluorescence-based method for the isolation of highly purified ventricular cardiomyocytes
ConclusionWe have developed a simple and reliable method for the isolation of highly purified vCMs from the adult murine myocardium, avoiding fixation and permeabilization steps. These isolated vCMs can be used in particular for detailed molecular studies, avoiding contamination with other myocardial cell types. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 14, 2017 Category: Cardiology Source Type: research

Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine
ConclusionsOur findings argue against low myocardial creatineper se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases. (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 11, 2017 Category: Cardiology Source Type: research

New dimensions in circadian clock function: the role of biological sex
(Source: Cardiovascular Research)
Source: Cardiovascular Research - December 11, 2017 Category: Cardiology Source Type: research

Relevance of low miR-30c-5p levels in atherogenesis: a promising predictive biomarker and potential therapeutic target
[Cardiovasc Res 2017;113(13):1536 –1537] (Source: Cardiovascular Research)
Source: Cardiovascular Research - December 9, 2017 Category: Cardiology Source Type: research

Endothelial permeability, LDL deposition, and cardiovascular risk factors —a review
AbstractEarly atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress. Mostly as a consequence of the activation of e...
Source: Cardiovascular Research - December 8, 2017 Category: Cardiology Source Type: research

Cbx3 inhibits vascular smooth muscle cell proliferation, migration, and neointima formation
ConclusionCbx3 modulates VSMC contractile and collagen gene expression, as well as VSMC proliferation, migration, and apoptosis via a Notch3 pathway, and plays an important role in controlling injury-induced neointima formation. (Source: Cardiovascular Research)
Source: Cardiovascular Research - November 30, 2017 Category: Cardiology Source Type: research

Regulation of low-density lipoprotein cholesterol by intestinal inflammation and the acute phase response
AbstractSystemic inflammation, induced by disease or experimental intervention, is well established to result in elevated levels of circulating triglycerides, and reduced levels of high-density lipoprotein-cholesterol (HDL-C), in most mammalian species. However, the relationship between inflammation and low-density lipoprotein-cholesterol (LDL-C) concentrations is less clear. Most reports indicate that systemic inflammation, as observed during sepsis or following high dose experimental endotoxaemia, lowers total, and LDL-C in man. However, isolated reports have suggested that certain inflammatory conditions are associated ...
Source: Cardiovascular Research - November 30, 2017 Category: Cardiology Source Type: research

Clinical and translational science in cardiovascular research: highlights from the American Heart Association Scientific Sessions 2017Changing view on the concept of cardiovascular risk and blood pressure targets
(Source: Cardiovascular Research)
Source: Cardiovascular Research - November 29, 2017 Category: Cardiology Source Type: research