AimsTo examine the metabolic adaptation to an 80-day exercise intervention in healthy young male adults where lifestyle factors such as diet, sleep, and physical activities are controlled. Methods and resultsThis study involved cross-sectional analysis before and after an 80-day aerobic and strength exercise intervention in 52 young, adult, male, newly enlisted soldiers in 2015. Plasma metabolomic

Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentrations of intracellular sodium, calcium and ATP/ADP. Here we review the diversity and

A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019

AimsB cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified. Methods and ResultsIn the present study, we show that follicular regulatory helper T cells (TFR) control regulatory B cell (BREG) populations in Apoe-/- mice models on a high-cholesterol diet (HCD). Feeding mice with HCD resulted in upregulation of TFR and BREG cell populations, causing

AimsThe G protein-coupled estrogen receptor 1 (GPER) may modulate some effects of aldosterone. Additionally, G-1 (a GPER agonist) can lower blood pressure (BP) and promote T cell-mediated anti-inflammatory responses. This study aimed to test the effects of G-1 and G-15 (a GPER antagonist) on aldosterone-induced hypertension in mice, and to examine the cellular mechanisms involved. Methods and ResultsC57Bl/6

A growing body of evidence indicates that cardiac regeneration after myocardial infarction can be achieved by stimulating the endogenous capacity of cardiomyocytes to replicate. This process is controlled, both positively and negatively, by a large set of non-coding RNAs. Some of the microRNAs (miRNAs) that can stimulate cardiomyocyte proliferation are expressed in embryonic stem cells and are required

Sepsis accounts for nearly 700,000 deaths in Europe annually is caused by an overwhelming host response to infection resulting in organ failure. The endothelium is an active contributor to sepsis and as such represents a major target for therapy. During sepsis, endothelial cells amplify the immune response and activate the coagulation system. They are both a target and source of inflammation and serve

AIMS B-cell lymphoma/leukemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II and antigen-dependent immune-cell activation to nuclear factor kappa-B (NF-κB) signaling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodeling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage

AIMS The myocardial ischemia/reperfusion (I/R) injury is almost inevitable since reperfusion is the only established treatment for acute myocardial infarction (AMI). To date there is no effective strategy available for reducing the I/R injury. Our aim was to elucidate the mechanisms underlying myocardial I/R injury and to develop a new strategy for attenuating the damage it causes. METHODS AND RESULTS

AIMS Cardiac fibrosis is a major cause of heart failure, and mediated by the differentiation of cardiac fibroblasts into myofibroblasts. However, limited tools are available to block cardiac fibrosis. ADAMTS16 is a member of the ADAMTS superfamily of extracellular protease enzymes involved in extracellular matrix degradation and remodeling. In this study, we aimed to establish ADAMTS16 as a key regulator

AIMS Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulation of monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific MR contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlates with aortic expansion in a murine model. The binding of Gd-TESMA to excised

AIMS The clinical application of doxorubicin is severely compromised by its cardiotoxic effects, which limit the therapeutic index and the cumulative dose. Liposomal encapsulation of doxorubicin (Myocet®) provides a certain protective effect against cardiotoxicity by reducing myocardial drug accumulation. We aimed to evaluate transcriptomic responses to anthracyclines with different cardiotoxicity

AIMS Adventitial remodeling presenting with the phenotypic switch of adventitial fibroblasts (AFs) to myofibroblasts (MFs) is reportedly involved in the evolution of several vascular diseases, including hypertension. In our previous study, we reported that heat shock protein 90 (HSP90) inhibition by 17-dime-thylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) markedly attenuates angiotensin II (AngII)-induced

AIMS Adaptive immunity contributes to the pathogenesis of cardiovascular metabolic disorders (CVMD). The omega-3 polyunsaturated fatty acids (n-3PUFA) are beneficial for cardiovascular health, with potential to improve the dysregulated adaptive immune responses associated with metabolic imbalance. We aimed to explore the mechanisms through which n-3PUFA may alter T cell motility and tissue distribution

AIMS Myocardial infarction (MI) leads to activation of cardiac fibroblasts (aCFs) and at the same time induces the formation of epicardium-derived cells at the heart surface. To discriminate between the two cell populations, we elaborated a fast and efficient protocol for the simultaneous isolation and characterization of aCFs and epicardial stromal cells (EpiSCs) from the infarcted mouse heart. METHODS

OBJECTIVE The elevated expression of phospholamban (PLB) has been observed in heart failure and cardiac remodeling, inhibiting the affinity of Ca2+ pump to Ca2+ thereby impairing heart relaxation. However, the mechanisms underlying the regulation of PLB remains to be further studied. The present study aims to test the role of RNA binding protein HuR in the regulation of PLB and the impact of this regulatory

AIMS Matrix metalloproteinase-2 (MMP-2) is a zinc dependent protease which contributes to cardiac contractile dysfunction when activated during myocardial ischemia-reperfusion (IR) injury. MMP-2 is localized to several subcellular sites inside cardiac myocytes, however, its role in the sarcoplasmic reticulum (SR) is unknown. The Ca2+ ATPase SERCA2a, which pumps cytosolic Ca2+ into the SR to facilitate

AIMS In mitral valve prolapse (MVP), leaflet thickening has recently been suggested to be due, in addition to a myxomatous degeneration, to the presence of a superimposed tissue (SIT), defined as an additional fibrous layer on top of the original leaflet. The mechanisms of SIT formation are currently unknown. We hypothesized that SIT formation would result from excessive leaflet stress and we used

AIMS Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease, and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. METHODS AND RESULTS We measured the expression of 10 miRs which were reportedly involved in calcification by using human aortic

Cardiovascular diseases are among the main causes of morbidity and mortality in Western countries and considered as a leading public health issue. Therefore, there is a strong need for new disease models to support the development of novel therapeutics approaches. The successive improvement of genome editing tools with zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs)

This review seeks to provide an update of preclinical findings and available clinical data on the chronic persistent inflammation and its direct role on the pulmonary arterial hypertension (PAH) progression. We reviewed the different mechanisms by which the inflammatory and immune pathways contribute to the structural and functional changes occurring in the three vascular compartments: the tunica intima

PCSK9 degrades LDL receptors and subsequently increases serum LDL-cholesterol. Clinical trials show that inhibition of PCSK9 efficiently lowers LDL-cholesterol levels and reduces cardiovascular events. PCSK9 inhibitors also reduce the extent of atherosclerosis. Recent studies show that PCSK9 is secreted by vascular endothelial cells, smooth muscle cells and macrophages. PCSK9 induces secretion of pro-inflammatory

This editorial refers to ‘B-cell lymphoma/leukemia 10 and angiotensin II-induced kidney injury’, by L. Markó et al., pp. 1059–1070.

This editorial refers to ‘Myocardial MMP-2 contributes to SERCA2a proteolysis during cardiac ischaemia-reperfusion injury’, by A. Roczkowsky et al., pp. 1021–1031.

[Cardiovasc Res 2019;115: e130–e132]

Type 2 diabetes mellitus (T2DM) is currently one of the most prevalent diseases, with as many as 415 million patients worldwide. T2DM is characterized by elevated blood glucose levels and is often accompanied by several comorbidities, such as cardiovascular disease. Treatment of T2DM is focused on reducing glucose levels by either lifestyle changes or medical treatment. One treatment option for T2DM

Corrigendum to: Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction [Cardiovasc Res 2014;(101): 97–107]

Gene editingHeart and muscle development and diseaseGene regulation

InflammationColchicineCoronary artery disease

Since 2014, CardioScape has been the most comprehensive database on cardiovascular research in Europe. The database aims to outline the current cardiovascular research and innovation landscape across Europe, providing information on the distribution and focus of funding in the cardiovascular field across Europe, and establishing the extent of duplication across national research programs and the existence

While the advent of drug-eluting stents has been clinically effective in substantially reducing the rates of major stent-related adverse events compared to bare metal stents, vascular biological problems such as neointimal hyperplasia, delayed re-endothelialisation, late stent thrombosis are not eliminated and, increasingly, neoatherosclerosis is the underlying mechanism for very late stent failure

AimsTelomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and upregulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere

CalciumArrhythmiaHeart failure PhospholambanHeart function

AimCardiac dysfunction is a prevalent comorbidity of disrupted inflammatory homeostasis observed in conditions such as sepsis (acute) or obesity (chronic). Secreted and transmembrane protein 1a (Sectm1a) has previously been implicated to regulate inflammatory responses, yet its role in inflammation-associated cardiac dysfunction is virtually unknown. Methods and resultsUsing the CRISPR/Cas9 system

AimsIn long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. Their recognition can improve risk stratification and clinical management, but their discovery represents a challenge. We tested whether a cellular-driven approach could help to identify new modifier genes and especially their mechanism of action. Methods and resultsWe generated

Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from hematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate

BackgroundRemote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal models of myocardial infarction. Platelet thrombus formation is a critical determinant of outcome in ST-segment elevation myocardial infarction (STEMI). Whether the beneficial effects of RIC are related to thrombotic parameters is unclear. Methods and ResultsIn a substudy of the Effect of Remote

VapingSmokingVascular functionPulmonary diseaseCancer

Runt-related transcription factor-1 (RUNX1), also known as acute myeloid leukaemia 1 protein (AML1), is a member of the core-binding factor family of transcription factors which modulate cell proliferation, differentiation, and survival in multiple systems. It is a master-regulator transcription factor, which has been implicated in diverse signalling pathways and cellular mechanisms during normal development

AimTo examine the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification). Methods and ResultsWe examined the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, COMPASS). The primary outcome

AIMS Cyclophilin-D is a well-known regulator of the mitochondrial permeability transition pore (PTP), the main effector of cardiac ischemia/reperfusion injury. However, the binding of CypD to the PTP is poorly understood. Cysteine 202 (C202) of CypD is highly conserved among species and can undergo redox-sensitive post-translational modifications. We investigated whether C202 regulates the opening

AIMS Long-term exposure of humans to air pollution enhances the risk of cardiovascular and respiratory diseases. A novel Global Exposure Mortality Model (GEMM) has been derived from many cohort studies, providing much-improved coverage of the exposure to fine particulate matter (PM2.5). We applied the GEMM to assess excess mortality attributable to ambient air pollution on a global scale and compare

Pulmonary arterial hypertension (PAH) is a disease with complex pathobiology, significant morbidity and mortality, and remains without a cure. It is characterized by vascular remodeling associated with uncontrolled proliferation of pulmonary artery smooth muscle cells, endothelial cell proliferation and dysfunction, and endothelial-to-mesenchymal transition, leading to narrowing of the vascular lumen

AIMS Endothelial cell (EC) homeostasis plays an important role in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodeling after myocardial infarction (MI). It has been shown that the sphingosine 1-phospahte receptor 1 (S1pr1) was highly expressed in ECs and played an important role in maintaining endothelial functions. We thus hypothesized

Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification

Contemporary data indicate that patients with signs and symptoms of ischaemia and non-obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) with elevated risk for adverse outcomes. Coronary endothelial (constriction with acetylcholine) and/or microvascular (limited coronary flow reserve with adenosine) dysfunction are well-documented, and extensive non-obstructive

AIMS Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI. METHODS AND RESULTS HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending

As nanotechnologies advance into clinical medicine, novel methods for applying nanomedicine to cardiovascular diseases are emerging. Extensive research has been undertaken to unlock the complex pathogenesis of atherosclerosis. However, this complexity presents challenges to develop effective imaging and therapeutic modalities for early diagnosis and acute intervention. The choice of ligand-receptor

AIMS Diabetes is a known risk factor for coronary artery disease. There is accumulating evidence that coronary artery disease pathogenesis differs for individuals with type 1 diabetes. However, the genetic background has not been extensively studied. We aimed to discover genetic loci increasing coronary artery disease susceptibility especially in type 1 diabetes, to examine the function of these discoveries

AIMS The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). METHODS AND RESULTS In this multicentre

AIM Adenosine receptors and extracellular adenosine have been demonstrated to modulate vascular smooth muscle cell (VSMC) proliferation and neointima formation. Adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels, but is function in VSMC remains unclear. Here, we investigated the role of ADK in vascular injury-induced smooth muscle proliferation and delineated the mechanisms

AIMS The cardiac ryanodine receptor (RyR2), which mediates intracellular Ca2+ release to trigger cardiomyocyte contraction, participates in development of acquired and inherited arrhythmogenic cardiac disease. This study was undertaken to characterize the network of inter- and intra-subunit interactions regulating the activity of the RyR2 homotetramer. METHODS AND RESULTS We use mutational investigations

AIMS SR-B1 is a cholesterol transporter that exerts anti-atherogenic properties in liver and peripheral tissues in mice. Bone marrow (BM) transfer studies suggested an atheroprotective role in cells of haematopoietic origin. Here, we addressed the specific contribution of SR-B1 in the monocyte/macrophage. METHODS AND RESULTS We generated mice deficient for SR-B1 in monocytes/macrophages (Lysm-Cre ×

AIMS Both progenitor and differentiated cells were previously shown to secrete cardioprotective substances, but so far there has been no direct comparison of the paracrine effects of the two cell types on heart failure. The study sought to compare the paracrine effect of selected progenitors and the corresponding non-progenitor mononuclear cardiac cells on the cardiac function of transgenic heart failure

AIMS The pathogenetic mechanisms underlying unprovoked venous thromboembolism (uVTE) are largely unknown. In this study, we investigated the molecular mechanisms involved in uVTE pathogenesis by using ex vivo expanded endothelial colony-forming cells (ECFCs), which represent a valuable non-invasive tool for the assessment of endothelial function. METHODS AND RESULTS We isolated and expanded ECFCs from