Clinical and cardiovascular magnetic resonance factors associated with elevated neutrophil-to-lymphocyte ratio in patients with heart failure: an analysis of a single-centre, prospective registry.

Objectives: The neutrophil-to-lymphocyte ratio (NLR) is defined as the ratio of neutrophils to lymphocytes measured in the full blood count. It has been studied across a range of conditions including cancer, sepsis and stroke. It has been proven that in patients with heart failure (HF) with reduced ejection fraction (HF-rEF), an elevated NLR reflects a higher risk of adverse outcomes.

Infection in people with heart failure: an overlooked cause of adverse outcomes.

Infections are a major cause of morbidity and mortality in people with heart failure, accounting for approximately 25% of hospitalisations and deaths. Infection hospitalisations in people with heart failure last twice as long as other hospitalisations, with mortality rates after discharge being comparable to those seen after acute decompensated heart failure. Addressing this major challenge is essential to further improving the survival and quality of life of this population.

PIEZO Force Sensors and the Heart.

The PIEZO1 and PIEZO2 membrane proteins form uniquely structured calcium permeable nonselective cation channels dedicated to mechanical force sensing in eukaryotic cells. In this review of the scientific literature, we address PIEZOs in the heart. PIEZOs enable the formation of the aortic valve, cardiac vasculature, and pericardial drainage.

Assessing LV Contractility Identifies Populations With Preserved Ejection Fraction at Risk of Adverse Heart Failure Outcomes.

Background: Left ventricular ejection fraction (LVEF) is an essential tool for heart failure (HF) assessment but is limited by load dependence. Additional tools are needed to risk-stratify normal LVEF populations. We aimed to assess the prognostic value of systolic blood pressure-indexed left ventricular end-systolic volume ratio, or cardiac contractility index (CCI).

variant implications for biological understanding and human health.

The large membrane protein PIEZO1 assembles as trimers to form exceptional mechanical force-sensing ion channels of eukaryotes. When these channels are activated by force, cell membrane permeability to calcium ions and other ions increases rapidly, coupling force to cell function through ionic control. In humans and other species, PIEZO1 is both widely expressed and functional across major systems that include the cardiovascular, haematological and musculoskeletal systems, thereby serving diverse needs.

Cardiovascular involvement in glycogen storage diseases.

Glycogen storage diseases are rare conditions affecting both sexes that are caused by inherited deficiencies of enzymes involved either in glycogen synthesis or breakdown, or in glycolysis. The liver and skeletal muscle are usually the most affected tissues. However, because glycogen has an important role in cardiac development and function, several glycogen storage diseases are associated, at least indirectly, with cardiac disorders, some of which have severe consequences from the first months of life.

Endothelial insulin-like growth factor-1 signalling regulates vascular barrier function and atherogenesis.

Aims: Progressive deposition of cholesterol in the arterial wall characterizes atherosclerosis, which underpins most cases of myocardial infarction and stroke. Insulin-like growth factor-1 (IGF-1) is a hormone that regulates systemic growth and metabolism and possesses anti-atherosclerotic properties. We asked whether endothelial-restricted augmentation of IGF-1 signalling is sufficient to suppress atherogenesis.

Application of CIBERSORTx and BayesPrism to deconvolution of bulk RNA-seq data from human myocardium and skeletal muscle.

RNA-sequencing (RNA-seq) is an important tool to explore molecular mechanisms of disease. Technological advances mean this can be performed at the single-cell level, but the large sample sizes needed in clinical studies are currently prohibitively expensive and complex. Deconvolution of bulk RNA-seq offers an opportunity to bridge this gap by defining the cell lineage composition of samples.

Comorbidity trajectories before and after the diagnosis of heart failure: A UK Biobank cohort study.

Aims: Heart failure (HF) is frequently associated with multiple comorbidities. We aimed to define their trajectory of accrual to identify opportunities for disease prevention.

Methods And Results: We identified all participants in the UK Biobank cohort study diagnosed with HF prior to enrolment or during follow-up, who had disease occurrence data available from both primary and secondary care records (n = 9824).

Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice.

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes.

Small molecule modulation of insulin receptor-insulin like growth factor-1 receptor heterodimers in human endothelial cells.

Objectives: The insulin receptor (IR) and insulin like growth factor-1 receptor (IGF-1R) are heterodimers consisting of two extracellular α-subunits and two transmembrane β -subunits. Insulin αβ and insulin like growth factor-1 αβ hemi-receptors can heterodimerize to form hybrids composed of one IR αβ and one IGF-1R αβ. The function of hybrids in the endothelium is unclear.

Insulin receptor signalling in PDGFRβ-expressing cells influences systemic metabolism and negatively impacts lipid storage.

Pericytes are vascular mural cells that support the microvasculature; their dysfunction contributes to diabetic retinopathy and has been linked to obesity in humans. To explore the role of pericyte insulin signalling on systemic metabolism we utilised male mice from our previously described PIR (PIRKO) mouse line which has insulin receptor (Insr) knockout in PDGFRβ-expressing cells. These animals exhibit systemic insulin resistance from as early as 8-weeks of age, despite no change in body weight or activity level, and show altered body composition and hepatosteatosis.

Echocardiographic screening for heart failure and optimization of the care pathway for individuals with pacemakers: a randomized controlled trial.

Individuals with pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). Whether screening for and optimizing the medical management of LVSD in these individuals can improve clinical outcomes is unknown. In the present study, in a multicenter controlled trial (OPT-PACE), we randomized 1,201 patients (717 men) with a pacemaker to echocardiography screening or usual care.

Distinct, common and synergistic effects of insulin and IGF-1 receptors on healthy murine ageing.

Objective: Reduced IGF-1 signalling is an evolutionarily conserved mediator of longevity, yet the magnitude of this effect is substantially larger in organisms retaining a common insulin and IGF-1 receptor. Whether this reflects the failure to simultaneously reduce IGF-1 and insulin signalling in mammalian model systems remains unexplored, as is the associated impact on markers of healthy ageing. We set out to address these uncertainties.

Plasma MERTK is causally associated with infection mortality.

Background: Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated.

Methods: We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants).

The diabetic myocardial transcriptome reveals Erbb3 and Hspa2 as a novel biomarkers of incident heart failure.

Aims: Diabetes mellitus (DM) increases heart failure incidence and worsens prognosis, but its molecular basis is poorly defined in humans. We aimed to define the diabetic myocardial transcriptome and validate hits in their circulating protein form to define disease mechanisms and biomarkers.

Methods And Results: RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project was used to define differentially expressed genes (DEGs) in right atrial (RA) and left ventricular (LV) myocardium from people with vs.

Studying Adipose Endothelial Cell/Adipocyte Cross-Talk in Human Subcutaneous Adipose Tissue.

Microvascular endothelial cells (MVECs) have many critical roles, including control of vascular tone, regulation of thrombosis, and angiogenesis. Significant heterogeneity in endothelial cell (EC) genotype and phenotype depends on their vascular bed and host disease state. The ability to isolate MVECs from tissue-specific vascular beds and individual patient groups offers the opportunity to directly compare MVEC function in different disease states.

Diabetes mellitus does not alter mortality or hospitalisation risk in patients with newly diagnosed heart failure with preserved ejection fraction: Time to rethink pathophysiological models of disease progression.

Introduction: Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established.

Methods: Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines.

Molecular mechanisms of diabetic heart disease: Insights from transcriptomic technologies.

Over half a billion adults across the world have diabetes mellitus (DM). This has a wide-ranging impact on their health, including more than doubling their risk of major cardiovascular events, in comparison to age-sex matched individuals without DM. Notably, the risk of heart failure is particularly increased, even when coronary artery disease and hypertension are not present.

Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.

Objective: Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes.

Research Design And Methods: A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status.

Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress.

Background & Aims: PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen.

Methods: Wall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non-disruptive tag in native PIEZO1 or endothelial-specific PIEZO1 deletion.