Matrix metalloproteinase-2 knockout prevents angiotensin II-induced vascular injury
ConclusionsMmp2 knockout impaired Ang II-induced vascular injury but not BP elevation. BM transplantation revealed a role for immune cells in Ang II-induced BP elevation, and for both vascular and immune cell MMP2 in Ang II-induced endothelial dysfunction. (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 20, 2017 Category: Cardiology Source Type: research

Human induced pluripotent stem cell-derived vascular smooth muscle cells: differentiation and therapeutic potential
AbstractCardiovascular diseases remain the leading cause of death worldwide and current treatment strategies have limited effect of disease progression. It would be desirable to have better models to study developmental and pathological processes and model vascular diseases in laboratory settings. To this end, human induced pluripotent stem cells (hiPSCs) have generated great enthusiasm, and have been a driving force for development of novel strategies in drug discovery and regenerative cell-therapy for the last decade. Hence, investigating the mechanisms underlying the differentiation of hiPSCs into specialized cell types...
Source: Cardiovascular Research - July 20, 2017 Category: Cardiology Source Type: research

Amyloidogenic medin induces endothelial dysfunction and vascular inflammation through the receptor for advanced glycation endproducts
AbstractAimsMedin is a common amyloidogenic protein in humans that accumulates in arteries with advanced age and has been implicated in vascular degeneration. Medin ’s effect on endothelial function remains unknown. The aims are to assess medin’s effects on human arteriole endothelial function and identify potential mechanisms underlying medin-induced vascular injury.Methods and resultsEx vivo human adipose and leptomeningeal arterioles were exposed (1  h) to medin (0.1, 1, or 5 µM) without or with FPS–ZM1 [100 µM, receptor for advanced glycation endproducts (RAGE)-specific in...
Source: Cardiovascular Research - July 20, 2017 Category: Cardiology Source Type: research

MicroRNA-532 protects the heart in acute myocardial infarction, and represses prss23, a positive regulator of endothelial-to-mesenchymal transition
ConclusionsIn conclusion, these findings reveal a pivotal role for miR-532-prss23 axis in regulating CEC function after MI, and this novel axis could be suitable for therapeutic intervention in ischemic heart disease. (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 11, 2017 Category: Cardiology Source Type: research

CCAAT/enhancer-binding protein delta promotes intracellular lipid accumulation in M1 macrophages of vascular lesions
ConclusionThis study underscores how CEBPD functions at the junction of inflammation and lipid accumulation in M1 macrophages. Therefore, CEBPD-mediated lipid accumulation in M1 macrophages could represent a new therapeutic target for the treatment of cardiovascular diseases. (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 11, 2017 Category: Cardiology Source Type: research

RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node
ConclusionsRHOA-ROCK signalling is involved in establishing the right-sided SAN as the definitive pacemaker of the heart and restricts typical pacemaker gene expression to the right side of the sinus venosus myocardium. (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 11, 2017 Category: Cardiology Source Type: research

Sirtuin 1 steers anti-inflammatory effects in vascular smooth muscle cells: protection without burden?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 4, 2017 Category: Cardiology Source Type: research

Tweak up-regulates endothelin-1 system in mouse and human endothelial cells
Corrigendum to: Tweak up-regulates endothelin-1 system in mouse and human endothelial cells [Cardiovasc Res 2017; 113 (2): 207-221] (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 4, 2017 Category: Cardiology Source Type: research

Insights into innate immune signalling in controlling cardiac remodelling
AbstractCanonical innate immune signalling involves complex cascades: multiple germline-encoded pattern recognition receptors rapidly recognize pathogen-associated or damage-associated molecular patterns to induce the production of cytokines, which bind to their corresponding receptors to orchestrate subsequent host defense phases. Inflammation is a healthy response to pathogenic signals, which are typically rapid and specific, and they terminate once the threat has passed. However, excessive activation or suppression of innate immune or inflammatory responses can lead to considerable human suffering, such as cardiac remod...
Source: Cardiovascular Research - July 3, 2017 Category: Cardiology Source Type: research

Impaired calcium homeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalent mouse model of the human HRC-Ser96Ala variant
ConclusionsThe homologous mutation Ser81Ala in HRC in mice, corresponding to Ser96Ala in humans, is associated with sudden death and depressed cardiac function. Ventricular arrhythmias are related to abnormal Ca2+ cycling across the SR. The data further support a role for CaMKII with the perspective to treat arrhythmias through CaMKII inhibition. (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 1, 2017 Category: Cardiology Source Type: research

DebULKing fat in the heart: a fascinating role for autophagy
(Source: Cardiovascular Research)
Source: Cardiovascular Research - June 28, 2017 Category: Cardiology Source Type: research

Angiotensin II infusion into ApoE -/- mice: a model for aortic dissection rather than abdominal aortic aneurysm?
ConclusionBased on our observations we propose an elaborate hypothesis that explains how aortic side branches (i) affect the initiation and propagation of medial tears and the subsequent adventitial dissection and (ii) affect the variability in shape of dissecting aneurysms. This hypothesis was partially validated through the live visualization of a dissecting aneurysm that formed during micro-CT imaging, and led us to the conclusion that angiotensin II-infused mice are more clinically relevant for the study of aortic dissections than for the study of abdominal aortic aneurysms. (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 27, 2017 Category: Cardiology Source Type: research

Surfactant protein D is not so friendly outside the lung-aggravation of cardiovascular disease
(Source: Cardiovascular Research)
Source: Cardiovascular Research - June 23, 2017 Category: Cardiology Source Type: research

Dr Fauconnier talks to genomics expert, Prof. McCarthy
Check the interview (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 22, 2017 Category: Cardiology Source Type: research

PCSK9 inhibition and clinical cardiovascular outcomes in patients with atherosclerotic cardiovascular disease
(Source: Cardiovascular Research)
Source: Cardiovascular Research - June 22, 2017 Category: Cardiology Source Type: research

Embracing the complexity of RNA regulatory networks: layer by layer
(Source: Cardiovascular Research)
Source: Cardiovascular Research - June 22, 2017 Category: Cardiology Source Type: research

Ventricular-arterial coupling in heart failure with preserved ejection fraction: the devil is in the details
This editorial refers to ‘Impact of acute hypertension transients on diastolic function in patients with heart failure with preserved ejection fraction’ by C. Pérez del Villaret al., pp. 906 –914 (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 22, 2017 Category: Cardiology Source Type: research

The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability
ConclusionThis study demonstrates that the T78M cav-3 induces complex modifications in ion channel function that ultimately alter membrane excitability. The presence of the T78M cav-3 can thus generate a susceptible substrate that, in concert with other structural alterations and/or genetic mutations, may become arrhythmogenic. (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 21, 2017 Category: Cardiology Source Type: research

Metabolic arithmetic: do two wrongs make a right?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - June 21, 2017 Category: Cardiology Source Type: research

Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis
ConclusionsThis study establishes that exosomes secreted by cardiomyocytes under ischaemic conditions promote heart angiogenesis, which may pave the way towards the development of add-on therapies to enhance myocardial blood supply. (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 19, 2017 Category: Cardiology Source Type: research

Uncovering the arrhythmogenic potential of TRPM4 activation in atrial-derived HL-1 cells using novel recording and numerical approaches
ConclusionsThese results collectively indicate that the TRPM4 channel is activated by a physiological range of Ca2+ concentrations and its excessive activity can cause arrhythmic changes. Moreover, these results demonstrate potential utility of the first AP models incorporating TRPM4 gating forin silico assessment of arrhythmogenicity in remodelling cardiac tissue. (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 19, 2017 Category: Cardiology Source Type: research

The role of perivascular adipose tissue-derived sensory nerves in influencing vascular regulation
This editorial refers to ‘Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilatation and leptin release’ by Bakaret al., pp. 962 –972. (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 15, 2017 Category: Cardiology Source Type: research

Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production
ConclusionsGF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1. (Source: Cardiovascular Research)
Source: Cardiovascular Research - June 5, 2017 Category: Cardiology Source Type: research

Serotonin and catecholamines in the development and progression of heart valve diseases
AbstractHeart valve diseases (HVDs) arise from a number of different processes that affect both the structure and function of the valve apparatus. Despite diverse aetiologies, treatments for HVDs are limited to percutaneous or surgical interventions. The search for medical therapies to prevent or slow the progression of HVDs has been hampered by our poor understanding of the progression from subclinical to symptomatic phases, and our limited knowledge of the molecular signals that control the susceptibility of valve interstitial cells to pathological remodeling. Clinical evidence has suggested a link between certain neurot...
Source: Cardiovascular Research - June 1, 2017 Category: Cardiology Source Type: research

Enhanced endothelin-1/Rho-kinase signalling and coronary microvascular dysfunction in hypertensive myocardial hypertrophy
ConclusionsMyocardial hypertrophy induced by pressure overload leads to cardiac and coronary microvascular dysfunction and ischaemia possibly due to oxidative stress, enhanced vasoconstriction to ET-1 and compromised endothelial NO function via elevated ROCK signalling. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 29, 2017 Category: Cardiology Source Type: research

Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations
ConclusionThe cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 26, 2017 Category: Cardiology Source Type: research

Distinguish mutation-specific pathogenic effects from secondary disease remodelling: an essential but often overlooked concept
(Source: Cardiovascular Research)
Source: Cardiovascular Research - May 25, 2017 Category: Cardiology Source Type: research

Myocardial fibrosis in response to pressure overload: elucidating the contribution of tissue transglutaminase
This editorial refers to ‘Tissue transglutaminase induction in the pressure-overloaded myocardium regulates matrix remodelling’, by A.V. Shindeet al., pp. 892 –905. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 25, 2017 Category: Cardiology Source Type: research

Heterogenous treatment effects: secrets for a reliable treat-to-target trial?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - May 17, 2017 Category: Cardiology Source Type: research

New role for CD36 in metastasis through fat intake
(Source: Cardiovascular Research)
Source: Cardiovascular Research - May 17, 2017 Category: Cardiology Source Type: research

A virtual issue for the CBCS Summer School 2017: focus on hot topics
The Council on Basic Cardiovascular Science (CBCS) Summer School, now in its 5th edition, keeps attracting the best young scientists to the ESC Heart House for five exciting days of science, networking, and career building (https://www.escardio.org/Education/Courses/Organised/Basic-science-summer-school). With a faculty of 26 for 70 participants, interactions between the more senior and junior colleagues are intense and rewarding. The leadership and organization includes the Scientists of Tomorrow, ensuring that the program includes the priorities set out by the young community. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 17, 2017 Category: Cardiology Source Type: research

T-tubule remodelling disturbs localized β 2 -adrenergic signalling in rat ventricular myocytes during the progression of heart failure
ConclusionAlthough changes in T-tubule structure and β2AR-mediated cAMP signalling are significant even at 4-week post-MI, progression to the HF phenotype is not linear. At 8-week post-MI the loss of β2AR-mediated cAMP is temporarily reversed. Complete disorganization of β2AR-mediated cAMP signalling due to changes in functional receptor localization and cellular structure occurs at 16-week post-MI. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 13, 2017 Category: Cardiology Source Type: research

Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and activates stress responses
ConclusionThese findings support a key role for mitochondrial p32 protein in cardiac myocytes modulating mitochondrial translation and function, and thereby survival. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 11, 2017 Category: Cardiology Source Type: research

T-tubular collagen: a new player in mechanosensing and disease?
This editorial refers to ‘Increased collagen within the transverse tubules in human heart failure’ by D.J. Crossmanet al., pp.879 –891 (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 8, 2017 Category: Cardiology Source Type: research

Fgf21 is required for cardiac remodeling in pregnancy
ConclusionsDuring pregnancy, both systemic and cardiac-produced Fgf21 act on the heart, leading to the normal physiological cardiac changes that are associated with pregnancy. Thus, Fgf21 acts as an endocrine/autocrine factor required for cardiac remodeling response to gestation. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 4, 2017 Category: Cardiology Source Type: research

OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA –NF-κB pathway
ConclusionsOxLDL-LPA promotes an osteogenic program in the aortic valve through a LPAR1-RhoA/ROCK –p65 pS536 pathway. LPAR1 may represent a suitable target to prevent the progression of CAVS. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 4, 2017 Category: Cardiology Source Type: research

Increased passive stiffness promotes diastolic dysfunction despite improved Ca 2+ handling during left ventricular concentric hypertrophy
ConclusionIn the hypertrophied heart with preserved systolic function,in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 4, 2017 Category: Cardiology Source Type: research

Lung ultrasound as a translational approach for non-invasive assessment of heart failure with reduced or preserved ejection fraction in mice
ConclusionsThis novel approach in mouse models of cardiac disease enables for the first time to adequately diagnose HF non-invasively in mice with preserved or reduced ejection fraction, and will pave the way to a better understanding of HF and to the development of new therapeutic approaches. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 4, 2017 Category: Cardiology Source Type: research

Matricellular protein thrombospondin-1 in pulmonary hypertension: multiple pathways to disease
AbstractMatricellular proteins are secreted molecules that have affinities for both extracellular matrix and cell surface receptors. Through interaction with structural proteins and the cells that maintain the matrix these proteins can alter matrix strength. Matricellular proteins exert control on cell activity primarily through engagement of membrane receptors that mediate outside-in signaling. An example of this group is thrombospondin-1 (TSP1), first identified as a component of the secreted product of activated platelets. As a result, TSP1 was initially studied in relation to coagulation, growth factor signaling and an...
Source: Cardiovascular Research - May 4, 2017 Category: Cardiology Source Type: research

Sex in basic research: concepts in the cardiovascular field
Women and men, female and male animals and cells are biologically different, and acknowledgement of this fact is critical to advancing medicine. However, incorporating concepts of sex-specific analysis in basic research is largely neglected, introducing bias into translational findings, clinical concepts and drug development. Research funding agencies recently approached these issues but implementation of policy changes in the scientific community is still limited, probably due to deficits in concepts, knowledge and proper methodology. This expert review is based on the EUGenMed project (www.eugenmed.eu) developing a roadm...
Source: Cardiovascular Research - May 4, 2017 Category: Cardiology Source Type: research

Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure
ConclusionsActivation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1 β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were significantly higher in TAC + OXT compared with TAC animals. HR sensitivity, but not contractile sensitivity, to β-adrenergic stimulation was improved in TAC + OXT hearts. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 2, 2017 Category: Cardiology Source Type: research

Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice
ConclusionSP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality. (Source: Cardiovascular Research)
Source: Cardiovascular Research - May 2, 2017 Category: Cardiology Source Type: research

Delayed, oral pharmacological inhibition of calpains attenuates adverse post-infarction remodelling
ConclusionsOur data demonstrate for the first time that long-term calpain inhibition is possible with delayed oral treatment, attenuates adverse post-infarction remodelling, likely through prevention of NF- ĸB activation, and may be a promising therapeutic intervention to prevent adverse remodelling and heart failure in patients with acute myocardial infarction. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 29, 2017 Category: Cardiology Source Type: research

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart
Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemi...
Source: Cardiovascular Research - April 29, 2017 Category: Cardiology Source Type: research

Analysis of genes to predict the effects of proprotein convertase subtilisin/kexin type 9-inhibitors and statins
Commentary on ‘Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes’ by Ference BAet al., N Engl J Med 2016.1 (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 27, 2017 Category: Cardiology Source Type: research

Dr Smart talks to Prof Pries and Prof Dirnagl on animal experimentation in biomedical research
(Source: Cardiovascular Research)
Source: Cardiovascular Research - April 27, 2017 Category: Cardiology Source Type: research

Transfer of mitochondria after stroke: a new hope for cardioprotection coming from the brain?
Commentary on ‘Transfer of mitochondria from astrocytes to neurons after stroke’ by Hayakawa Ket al., Nature 2016.1 (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 27, 2017 Category: Cardiology Source Type: research

DNA methylome analysis reveals distinct epigenetic patterns of ascending aortic dissection and bicuspid aortic valve
ConclusionOur data supports a model in which increased cellular proliferation in AD and BAV underpins loss of methylation at non-CpG sites. Our data further supports a model, in which AD is associated with an inflammatory vascular remodeling process, possibly mediated by the epigenome and linked to environmental risk factors such as smoking. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 27, 2017 Category: Cardiology Source Type: research

Layer upon layer: the functional consequences of disrupting the glycocalyx-endothelial barrier in vivo and in vitro
This editorial refers to ‘Endothelial glycocalyx breakdown is mediated by angiopoietin-2’ by A. Lukaszet al., pp.671 –680. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 27, 2017 Category: Cardiology Source Type: research

Relaxin: reproductive safeguard turned cardiac?
This editorial refers to ‘Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy’ by J. Nonhoffet al., pp. 598 –608 and ‘Reperfusion therapy with recombinant human relaxin-2 (serelaxin) attenuates myocardial infarct size and NLRP3 inflammasome following ischaemia/reperfusion injury via eNOS-dependent mechanism’ by J. Valle Raleighet al., pp.609 –619. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 27, 2017 Category: Cardiology Source Type: research