MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1
ConclusionsThis study shows that miR-424(322) has diagnostic and prognostic value in PH patients, correlating with markers of disease severity. Additionally, miR-424(322) can target proteins with a direct effect on heart function, suggesting that this miRNA can act as a messenger linking pulmonary vascular disease and right ventricle hypertrophy. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 12, 2017 Category: Cardiology Source Type: research

Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability
AbstractAimsIn patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, high pro-inflammatory chemokines, and low differentiation ability. As dapagliflozin reduces body fat and cardiovascular events in diabetic patients, we would like to know its effect on EAT and subcutaneous adipose tissue (SAT).Methods and resultsAdipose samples were obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter 2 (SGLT2) expression was determined by real-time polymerase chain reaction (n = 20), western blot, and immunohistochemistry. Fat explants (n&th...
Source: Cardiovascular Research - September 11, 2017 Category: Cardiology Source Type: research

CXCL12-CXCR4 signalling plays an essential role in proper patterning of aortic arch and pulmonary arteries
ConclusionCXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries inCxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 11, 2017 Category: Cardiology Source Type: research

Diverging effects of enalapril or eplerenone in primary prevention against doxorubicin-induced cardiotoxicity
ConclusionEnalapril and eplerenone disparately impact on cellular signalling in DIC. Eplerenone, on top of Dox treatment was not protective and associated with increased levels of plasma aldosterone and of cardiac CTGF. In contrast, we show that primary prevention with enalapril preserves LV morphology and function in a clinically relevant model of chronic DIC, with increased stimulation of the PI3K/AKT/mTOR axis and normal CTGF levels suggesting potential therapeutic implications. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 7, 2017 Category: Cardiology Source Type: research

Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1
ConclusionVascular dysfunctions in diet-induced obesity are prevented by deletion of arginase 1 in vascular endothelial cells or arginase inhibition. These findings indicate that upregulation of arginase 1 expression/activity in vascular endothelial cells has an integral role in diet-induced cardiovascular dysfunction and metabolic syndrome. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 7, 2017 Category: Cardiology Source Type: research

A novel fibroblast growth factor-1 ligand with reduced heparin binding protects the heart against ischemia-reperfusion injury in the presence of heparin co-administration
AbstractAimsFibroblast growth factor 1 (FGF1), a heparin/heparan sulfate-binding growth factor, is a potent cardioprotective agent against myocardial infarction (MI). The impact of heparin, the standard of care for MI patients entering the emergency room, on cardioprotective effects of FGF1 is unknown, however.Methods and resultsTo address this, a rat model of MI was employed to compare cardioprotective potentials (lower infarct size and improve post-ischemic function) of native FGF1 and an engineered FGF1 (FGF1ΔHBS) with reduced heparin-binding affinity when given at the onset of reperfusion in the absence or presen...
Source: Cardiovascular Research - September 7, 2017 Category: Cardiology Source Type: research

Endothelial to haematopoietic transition contributes to pulmonary arterial hypertension
ConclusionEHT contributes to the pathogenesis of PAH. The transcription factor Runx1 may be a novel therapeutic target for the treatment of PAH. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 7, 2017 Category: Cardiology Source Type: research

Regulation of vascular smooth muscle cell calcification by syndecan-4/FGF-2/PKC α signalling and cross-talk with TGFβ
ConclusionThis is the first demonstration that syndecan-4 promotes FGF-2 signalling, and in turn, suppresses VSMC mineralization by down-regulating TGF β signalling. Our discoveries that FGF-2 and syndecan-4 expression is increased in mineralizing VSMCs and that PKCα regulates FGF-2 and TGFβ signalling in VSMCs suggests that the syndecan-4/FGF-2/TGFβ signalling axis could represent a new therapeutic target for vascular calcification. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 6, 2017 Category: Cardiology Source Type: research

Treatment strategies for the right heart in pulmonary hypertension
AbstractThe function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the main determinant of changes to the ventricle. Secondly, we discuss treatment strategies targeting the detrimental consequences of increased RV wall stress. To reduce wall stress, afterload reduction is the essential. Additionally, preload to the ventricle can be reduced by d...
Source: Cardiovascular Research - September 5, 2017 Category: Cardiology Source Type: research

LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification
ConclusionAll together, the evidence generated by our study elucidates the role of lncRNA TUG1 as a miRNA sponge in CAVD, and sheds new light on lncRNA-directed diagnostics and therapeutics in CAVD. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 4, 2017 Category: Cardiology Source Type: research

Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype of atherosclerotic plaques with high collagen content
ConclusionIn this study, we demonstrate that TRIM21 influences atherosclerosis via regulation of Th17 responses, with TRIM21 deficiency promoting IL-17 expression and a more fibrous, stable, phenotype of the plaques. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 4, 2017 Category: Cardiology Source Type: research

Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation
ConclusionThese findings reveal previously unrecognized characteristics and complexity of platelets and their regulation of adhesion/aggregation. The identification of platelet subpopulations also has potentially important consequences to human health and disease as impaired platelet NO-signalling has been identified in patients with coronary artery disease. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 4, 2017 Category: Cardiology Source Type: research

A focus on the greatness of the lesser circulation: spotlight issue on the right ventricle
What is the motivation behind a special issue on the right ventricle? William Harvey ’s assertion in 1628 that ‘(mother nature) would not have added the right ventricle for the sole purpose of nourishing the lungs, but to propel blood through the lungs into the cavity of the LV’1 celebrated the marvel of human physiology in which all constituents have an important function. The right ventricle (RV) is of critical importance. The circulation is composed of a single continuous circuit in which there are only two intrinsic contractile pumps; the RV that provides the pressure necessary to augment flow through...
Source: Cardiovascular Research - September 4, 2017 Category: Cardiology Source Type: research

Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart
ConclusionMyofibroblasts contribute to the population of electrically coupled nonmyocytes in the infarct border zone. The slower kinetics of myofibroblast voltage responses may reflect low electrical conductivity across heterocellular junctions, in accordance with the paucity of connexin expression at myofibroblast-cardiomyocyte contacts. (Source: Cardiovascular Research)
Source: Cardiovascular Research - September 1, 2017 Category: Cardiology Source Type: research

Cgnl1, an endothelial junction complex protein, regulates GTPase mediated angiogenesis
ConclusionsOur data demonstrate a functional relevance for Cgnl1 as a defining factor in new vessel formation bothin vitro andin vivo. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 31, 2017 Category: Cardiology Source Type: research

The HAND1 frameshift A126FS mutation does not cause hypoplastic left heart syndrome in mice
ConclusionsSomatically acquiredHand1A126FS mutation is not causative of HLHS.Hand1A126FS mutation does exhibit embryonic lethal cardiac defects that reflect a dominant negative function supporting the critical role of Hand1 in cardiogenesis. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 31, 2017 Category: Cardiology Source Type: research

Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells
ConclusionCKD aggravates vein graft disease through mechanisms involving IL-9 and mast cell activation. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 31, 2017 Category: Cardiology Source Type: research

Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies
ConclusionCa2+ fluxes in isolated cardiomyocytes show so much clustering that the common statistical approach that assumes independence of each data point will frequently give the false appearance of statistically significant changes. Hierarchical statistical methodologies need a little more effort, but are necessary for reliable conclusions. We present cost-free simple tools for performing these analyses. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 30, 2017 Category: Cardiology Source Type: research

Origins and consequences of congenital heart defects affecting the right ventricle
AbstractCongenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventri...
Source: Cardiovascular Research - August 30, 2017 Category: Cardiology Source Type: research

Low-energy defibrillation with nanosecond electric shocks
ConclusionNanosecond-defibrillation is a promising technology that may allow clinical defibrillation with profoundly reduced energies. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 29, 2017 Category: Cardiology Source Type: research

Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts
ConclusionTCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation of atrial fibrillation particularly in HF. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 29, 2017 Category: Cardiology Source Type: research

Investigation of cardiac fibroblasts using myocardial slices
AbstractAimsCardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and culturedin vitro, CFs undergo rapid phenotypic changes including increased expression of α-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli usingin vitro cultured mouse, dog and human myocardial slices.Methods and resultsUnloading of myocardial slices induced CF proliferation without α-SMA expression up to 7 daysin culture. CFs migrating onto the culture plastic support...
Source: Cardiovascular Research - August 18, 2017 Category: Cardiology Source Type: research

IL-10 reprogramming of metabolism in macrophages through mitophagy
(Source: Cardiovascular Research)
Source: Cardiovascular Research - August 18, 2017 Category: Cardiology Source Type: research

Cardiovascular benefits and risks of testosterone replacement: another warning?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - August 18, 2017 Category: Cardiology Source Type: research

Sonic hedgehog-dependent activation of adventitial fibroblasts promotes neointima formation
ConclusionsThe initial activation of adventitial fibroblasts is essential for the subsequent proliferation of SMC and neointima formation. We identified SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 16, 2017 Category: Cardiology Source Type: research

miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways
ConclusionsWith an unbiased screening of secreted microRNAs, we identify reduction of miR-30c-5p in microparticles as a promoter of early atherosclerosis, by conveying pro-inflammatory pro-apoptotic signals and impairing endothelial healing. Therefore, stimulation of miR-30c-5p is a candidate direct anti-atherosclerotic therapy. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 14, 2017 Category: Cardiology Source Type: research

Exercise and the right ventricle: a potential Achilles ’ heel
AbstractExercise is associated with unequivocal health benefits and results in many structural and functional changes of the myocardium that enhance performance and prevent heart failure. However, intense exercise also presents a significant hemodynamic challenge in which the right-sided heart chambers are exposed to a disproportionate increase in afterload and wall stress that can manifest as myocardial fatigue or even damage if intense exercise is sustained for prolonged periods. This review focuses on the physiological factors that result in a disproportionate load on the right ventricle during exercise and the long-ter...
Source: Cardiovascular Research - August 14, 2017 Category: Cardiology Source Type: research

Combining computer modelling and cardiac imaging to understand right ventricular pump function
AbstractRight ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump fu...
Source: Cardiovascular Research - August 14, 2017 Category: Cardiology Source Type: research

The overloaded right heart and ventricular interdependence
AbstractThe right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hyperten...
Source: Cardiovascular Research - August 14, 2017 Category: Cardiology Source Type: research

Role of cardiac inflammation in right ventricular failure
AbstractRight ventricular failure (RVF) is the main determinant of mortality in patients with pulmonary arterial hypertension (PAH). Although the exact pathophysiology underlying RVF remains unclear, inflammation may play an important role, as it does in left heart failure. Perivascular pulmonary artery and systemic inflammation is relatively well studied and known to contribute to the initiation and maintenance of the pulmonary vascular insult in PAH. However, less attention has been paid to the role of cardiac inflammation in RVF and PAH. Consistent with many other types of heart failure, cardiac inflammation, triggered ...
Source: Cardiovascular Research - August 14, 2017 Category: Cardiology Source Type: research

MicroRNAs in right ventricular remodelling
AbstractRight ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to dise...
Source: Cardiovascular Research - August 14, 2017 Category: Cardiology Source Type: research

Cardiac effects of SGLT2 inhibitors: the sodium hypothesis
AbstractThe effects of intense glycaemic control on macrovascular complications in patients with type 2 diabetes are incompletely resolved, and many glucose-lowering medications negatively affect cardiovascular outcomes. Recently, the EMPA-REG OUTCOME trial revealed that empagliflozin, an inhibitor of the sodium-glucose cotransporter 2 (SGLT2), substantially reduced the risk of hospitalization for heart failure, death from cardiovascular causes, and all-cause mortality in patients with type 2 diabetes mellitus at high cardiovascular risk. Although several mechanisms may explain this benefit, plasma volume contraction and a...
Source: Cardiovascular Research - August 4, 2017 Category: Cardiology Source Type: research

β-arrestin 2 mediates cardiac ischemia-reperfusion injury via inhibiting GPCR-independent cell survival signalling
ConclusionWe define an upregulation of Arrb2 as a pathogenic factor in cardiac I/R injury, and also reveal a novel GPCR-independent mechanism of Arrb2-mediated cell death signalling in the heart. (Source: Cardiovascular Research)
Source: Cardiovascular Research - August 4, 2017 Category: Cardiology Source Type: research

Arrhythmogenic cardiomyopathy: pathology, genetics, and concepts in pathogenesis
AbstractArrhythmogenic cardiomyopathy (ACM) is a rare, heritable heart disease characterized by fibro-fatty replacement of the myocardium and a high degree of electric instability. It was first thought to be a congenital disorder, but is now regarded as a dystrophic heart muscle disease that develops over time. There is no curative treatment and current treatment strategies focus on attenuating the symptoms, slowing disease progression, and preventing life-threatening arrhythmias and sudden cardiac death. Identification of mutations in genes encoding desmosomal proteins and in other genes has led to insights into the disea...
Source: Cardiovascular Research - August 4, 2017 Category: Cardiology Source Type: research

Fibroblasts and the extracellular matrix in right ventricular disease
AbstractRight ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix protein...
Source: Cardiovascular Research - August 4, 2017 Category: Cardiology Source Type: research

Tilting at the tilted protease balance in arterial aneurysmal disease
(Source: Cardiovascular Research)
Source: Cardiovascular Research - August 4, 2017 Category: Cardiology Source Type: research

RV pressure overload: from hypertrophy to failure
AbstractIn pulmonary arterial hypertension (PAH), right ventricular (RV) adaptation is essential to overcome the chronic increases in RV pressure overload. Ultimately, RV compensatory mechanisms are not sufficient and patients succumb to RV failure. The processes underlying the transition of RV adaptation to RV failure are not well understood. In this review, we propose that important insights in RV adaptation processes can be obtained by comparing different etiologies of PAH, namely patients with PAH secondary to Eisenmenger syndrome, patients with PAH secondary to systemic sclerosis and patients where no cause is identif...
Source: Cardiovascular Research - August 2, 2017 Category: Cardiology Source Type: research

Context-dependent signalling in platelets in vascular diseases: ROCK2 around thrombosis
(Source: Cardiovascular Research)
Source: Cardiovascular Research - August 2, 2017 Category: Cardiology Source Type: research

Melatonin as a cardioprotective therapy following ST-segment elevation myocardial infarction: is it really promising? Reply
We thank Dominguez-Rodriguez and Abreu-Gonzalez1 for their comment on our ESC Working Group (WG) Position Paper on cardioprotection,2 in which they propose melatonin to be a promising cardioprotective strategy. This was based, in part, on the recently published results of the Melatonin Adjunct in acute myocaRdial Infarction treated with Angioplasty (MARIA) trial, in which they investigated the cardioprotective effects of melatonin in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI).3 However, in the MARIA trial, the authors found that intravenous and i...
Source: Cardiovascular Research - July 28, 2017 Category: Cardiology Source Type: research

Future strategies for acute cardioprotection: ‘melatonin as promising therapy’
To the Editor, (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 28, 2017 Category: Cardiology Source Type: research

From drugs to devices and back again: chemical vagal nerve stimulation for the treatment of heart failure
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

The science of stents: angioplasty turns 40
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

Improving the outcome of primary PCI: protection from reperfusion injury
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

Young researchers enjoying great science and good company in the south of France in summer!
Abstract (Source: Cardiovascular Research)
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

Network medicine: a new paradigm for cardiovascular disease research and beyond
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

The unexpected intelligence: what is the naked mole –rat’s secret to surviving oxygen deprivation?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

A role for autoantibodies in atherogenesis
AbstractAn increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the associa...
Source: Cardiovascular Research - July 27, 2017 Category: Cardiology Source Type: research

Etv2 as an essential regulator of mesodermal lineage development
AbstractThe ‘master regulatory factors’ that position at the top of the genetic hierarchy of lineage determination have been a focus of intense interest, and have been investigated in various systems. Etv2/Etsrp71/ER71 is such a factor that is both necessary and sufficient for the development of haematopoie tic and endothelial lineages. As such, genetic ablation of Etv2 leads to complete loss of blood and vessels, and overexpression can convert non-endothelial cells to the endothelial lineage. Understanding such master regulatory role of a lineage is not only a fundamental quest in developmental biolog y, but a...
Source: Cardiovascular Research - July 26, 2017 Category: Cardiology Source Type: research

Bioactive lipids in aortic valve stenosis —a possible link to atherosclerosis?
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 25, 2017 Category: Cardiology Source Type: research

ROCK as a molecular bond connecting coronary microvascular and cardiac remodelling
(Source: Cardiovascular Research)
Source: Cardiovascular Research - July 24, 2017 Category: Cardiology Source Type: research