Meteorin-like protein plasma levels are associated with worse outcomes in de novo heart failure.

Background And Aims: Meteorin-like protein (Metrnl) has been recently suggested as a new adipokine with protective cardiovascular effects. Its circulating levels in patients seem to be associated with heart failure (HF), although with contradictory results. Our aim was to ascertain whether this adipokine could estimate the prognosis of HF in de novo HF (DNHF) patients.

Multimodal data-based longitudinal prognostic model for predicting atrial fibrillation recurrence after catheter ablation in patients with patent foramen ovale and paroxysmal atrial fibrillation.

Background: Clinical studies on atrial fibrillation (AF) recurrence after catheter ablation in patients diagnosed with patent foramen ovale (PFO) and paroxysmal AF (PAF) are scarce. Here, we aimed to develop a nomogram model utilizing multimodal data for the risk stratification of AF recurrence following catheter ablation in individuals diagnosed with PFO and new-onset PAF.

Methods: Patients with PFO and PAF who underwent catheter ablation at the Renmin Hospital of Wuhan University from January 2018 to June 2020 were consecutively enrolled.

Arbovirus exposure and subclinical myocardial dysfunction in an Indigenous population in Northeast Brazil: a cross-sectional study.

Background: Human activities, such as urbanization and climate change, have facilitated the spread of arbovirus-carrying vectors, disproportionately affecting vulnerable traditional Indigenous communities.

Objective: To explore the relationships between subclinical myocardial dysfunction, assessed by global longitudinal strain (GLS), and comprehensive arbovirus serology in an Indigenous population, while also describing the serological and epidemiological profile of dengue, chikungunya, and Zika viruses.

Methods: This ancillary study is part of the first phase (2016-2017) of the Project of Atherosclerosis among Indigenous Populations (PAI), a cross-sectional study involving participants from two Indigenous communities with different degrees of urbanization and a highly urbanized city in Northeast Brazil.

Serotonin receptor 5-HT7 modulates inflammatory-associated functions of macrophages.

The hormone and neurotransmitter serotonin regulates numerous physiological functions within the central nervous system and in the periphery upon binding to specific receptors. In the periphery, the serotonin receptor 7 (5-HT7R) is expressed on different immune cells including monocytes and macrophages. To investigate the impact of 5-HT7R-mediated signaling on macrophage properties, we used human THP-1 cells and differentiated them into pro-inflammatory M1- and anti-inflammatory M2-like macrophages.

Risk factors for non-benefit of implantable cardioverter defibrillator therapy.

Studies have demonstrated overall prognostic benefits of ICD implantation in patients at increased risk of sudden cardiac death. However, results are inconsistent in certain subgroups. This study aims to evaluate the prognostic implications of comorbidities on ICD outcomes and compare trends in patient selection and outcomes over a decade-long inclusion period.

JOSD2 inhibits angiotensin II-induced vascular remodeling by deubiquitinating and stabilizing SMAD7.

Increased level of angiotensin II (Ang II) plays a central role in the development of hypertensive vascular remodeling. In this study, we identified the deubiquitinating enzyme Josephin domain-containing protein 2 (JOSD2) as a protective factor and investigated its molecular mechanism in Ang II-induced vascular remodeling. First, we found that JOSD2 was upregulated in aortic smooth muscle cells, but not in endothelial cells of Ang II-challenged mouse vascular tissues.

Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry.

Aims: This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.

Methods And Results: Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models.

Downregulation of CCR2 reduces ventricular remodeling after myocardial infarction by splenic nerve neuromodulation in acute and chronic rat models.

Objectives: Pathological remodeling after myocardial infarction (MI) confers the development of heart failure. Our prior research has indicated that splenic nerve neuromodulation mitigates myocardial ischemia-reperfusion injury (IRI) by reducing levels of proinflammatory factors. This study aims to explore the potential therapeutic benefits of splenic nerve neuromodulation in MI and the underlying mechanism.

Differential transcriptomic profiling of lipid metabolism and collagen remodeling in fast- and slow-twitch skeletal muscles in aging.

Skeletal muscle function gradually declines with aging, presenting substantial health and societal challenges. Comparative analysis of how aging affects fast- and slow-twitch muscles remains lacking. We utilized 20-month-old mice to reveal the aging effects on muscle structure and fiber composition, followed by bulk RNA sequencing for fast- and slow-twitch muscles and integration with human single-cell RNA sequencing dataset providing a comparative analysis across species.

Associations Between Complement C4, Habitual Constipation, and Sleep Disturbance in Oldest-Old and Centenarian Chinese Adults.

Background: Sleep disturbance is an immune-related disease, and the gut-brain axis is an important regulatory pathway. This cross-sectional study was designed to address these associations between complement C4, habitual constipation, and sleep disturbance and presents a reference for prevention and treatment of sleep disturbance.

Methods: Based on the China Hainan Centenarian Cohort Study, Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep disturbance following standard procedure.

Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE.

Aims: Despite receiving guideline-directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH-LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long-acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile.

Association between epigenetic aging and atrioventricular block: a two-sample Mendelian randomization study.

Aims: Atrioventricular block (AVB) is a prevalent bradyarrhythmia. This study aims to investigate the causal effects of epigenetic aging, as inferred from DNA methylation profiles on the prevalence of AVB by Mendelian randomization (MR) analysis.

Methods: Genetic instruments for epigenetic aging and AVB were obtained from genome-wide association study data in the Edinburgh DataShare and FinnGen biobanks.

Berberine Inhibited SASP-Related Inflammation through RXR[Formula: see text]/PPAR[Formula: see text]/NEDD4 Pathway in Atherosclerosis.

The accumulation of aging cells significantly contributes to chronic inflammatory diseases such as atherosclerosis. Human carotid artery single-cell sequencing has shown that large numbers of aging foam cells are present in the plaques of human patients. Berberine (BBR) has been shown to inhibit cell senescence, however, the mechanisms involved in its treatment of atherosclerotic senescence have not yet been determined.

Protective Effects of Melatonin on Kidney Function Against Contrast Media-Induced Kidney Damage in Patients With Chronic Kidney Disease: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.

Patients with chronic kidney disease (CKD) are at increased risk of acute kidney injury following exposure to contrast media. We evaluated the effect of melatonin, a potent antioxidant, as a protective strategy against contrast-induced acute kidney injury (CI-AKI), with a focus on molecular mechanisms. We randomized patients with an eGFR < 60 mL/min/1.

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n = 4) from those without (n = 7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD.

Aspirin-free strategies after percutaneous coronary intervention: Old habits, consolidated evidence and future perspectives.

For almost two decades, dual antiplatelet therapy (DAPT) has been considered the cornerstone of pharmacological treatment in patients undergoing percutaneous coronary intervention (PCI). DAPT composition and duration have considerably evolved in the last decade moving from fixed treatment durations to tailored strategies based on the individual ischemic and bleeding risks. The increasing awareness of the prognostic relevance of bleeding events after PCI and the need for tailoring DAPT according to the individual bleeding and ischemic risks paved the way to newer DAPT modulation strategies by early aspirin withdrawal which have been shown to decrease bleeding without affecting therapeutic efficacy.

Sex and age distribution of global disease burden of non-rheumatic calcific aortic valve disease from 1990 to 2021.

Objectives: To analyze sex and age distribution of global disease burden of non-rheumatic calcific aortic valve disease (CAVD) from 1990 to 2021.

Methods: CAVD data 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups.

S1PR3 in hippocampal neurons improves synaptic plasticity and decreases depressive behavior via downregulation of RhoA/ROCK1.

The study investigates how Sphingosine-1-phosphate receptor 3 (S1PR3) and the Chronic Unpredictable Mild Stress (CUMS) affects depression-like behaviors. The S1P/S1PR3 signaling pathway is known to play a role in mood regulation, but it is not yet fully understood how it is connected to depression. This study looks to further explore this topic.

LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.

Background: The genetic variants of LMNA cause an array of diseases that often affect the heart. LMNA-related cardiomyopathy exhibits high-penetrance and early-onset phenotypes that lead to late-stage heart failure or lethal arrhythmia. As a subtype of dilated cardiomyopathy and arrhythmogenic cardiomyopathy, LMNA-related cardiac dysfunction is resistant to existing cardiac therapeutic strategies, leaving a major unmet clinical need in cardiomyopathy management.

Caloric restriction and its mimetics in heart failure with preserved ejection fraction: mechanisms and therapeutic potential.

The global increase in human life expectancy, coupled with an unprecedented rise in the prevalence of obesity, has led to a growing clinical and socioeconomic burden of heart failure with preserved ejection fraction (HFpEF). Mechanistically, the molecular and cellular hallmarks of aging are omnipresent in HFpEF and are further exacerbated by obesity and associated metabolic diseases. Conversely, weight loss strategies, particularly caloric restriction, have shown promise in improving health status in patients with HFpEF and are considered the gold standard for promoting longevity and healthspan (disease-free lifetime) in model organisms.

Generation of an isogenic CRISPR/Cas9-corrected control induced pluripotent stem cell line from a patient with autosomal dominant catecholaminergic polymorphic ventricular tachycardia with a heterozygous variant in cardiac calsequestrin-2.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease characterised by adrenergic-induced arrhythmias. The leading causes of CPVT are pathogenic variants in cardiac ryanodine receptor 2 (RYR2) and rarely, in cardiac calsequestrin-2 (CASQ2) genes, which are major components of Ca handling in cardiac myocytes. This resource builds upon an established induced pluripotent stem cell line generated from a family with autosomal dominant CPVT due to a heterozygous variant in CASQ2 c.

Epigenome-wide association study of perceived discrimination in the Multi-Ethnic Study of Atherosclerosis (MESA).

Perceived discrimination, recognized as a chronic psychosocial stressor, has adverse consequences on health. DNA methylation (DNAm) may be a potential mechanism by which stressors get embedded into the human body at the molecular level and subsequently affect health outcomes. However, relatively little is known about the effects of perceived discrimination on DNAm.

miR-199a-3p mitigates simulated microgravity-induced cardiac remodeling by targeting MEF2C.

Microgravity-induced cardiac remodeling and dysfunction present significant challenges to long-term spaceflight, highlighting the urgent need to elucidate the underlying molecular mechanisms and develop precise countermeasures. Previous studies have outlined the important role of miRNAs in cardiovascular disease progression, with miR-199a-3p playing a crucial role in myocardial injury repair and the maintenance of cardiac function. However, the specific role and expression pattern of miR-199a-3p in microgravity-induced cardiac remodeling remain unclear.

Sotatercept in pulmonary hypertension and beyond.

Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2.