Obesity is one of the biggest risks to public health in both developed and developing countries, and yet incidence continues to skyrocket. Being the main risk factor for a large number of life-limiting conditions, obesity has the potential to cause enormous damage unless addressed urgently. Heart failure (HF) is the most common cardiovascular disease associated with obesity. The incidence of HF overall

Aims LIPC encodes hepatic lipase (HL), a liver-bound protein with both phospholipase and triglyceride lipase activity, and involved in the catabolism of circulating lipoproteins. We recently identified the gain-of-function variant HL-E97G, with selectively increased phospholipase activity, as a new genetic cause of familial combined hypocholesterolemia in humans. The role of HL in the development of

Aims Platelets contain non-coding RNAs (ncRNAs), and their measurement may complement platelet aggregometry. Methods and results In the community-based Bruneck Study (n = 338), we generated platelet-rich plasma (PRP), platelet-poor plasma (PPP) and platelets. PRP was subjected to aggregometry using various agonists and processed to platelet releasates thereafter. Releasates, PPP and platelets underwent

Aims A comprehensive understanding of the genome-wide regulatory landscape of the cardiac tissues post-myocardial infarction (MI) is still lacking. We therefore integrated single-cell RNA sequencing (scRNA-seq) and single-cell for transposase-accessible chromatin sequencing (scATAC-seq) to elucidate the epigenetic landscape of the heart post-MI. Methods and results We established MI mice through ligation

Ceramides are bioactive lipid mediators involved in apoptosis, inflammation, and fibrosis. This narrative review provides a concise overview of the emerging role of ceramides in cardiovascular disease with emphasis on atherosclerotic vascular disease and heart failure, suggesting a potential use of ceramides in risk stratification and as putative therapeutic targets. Recent developments based on observational

Aims Antibody Drug Conjugates(ADCs) are approved for use in cancers. Cardiovascular adverse reaction is a fatal adverse reactions associated with ADCs. The incidence of adverse cardiac events about ADCs have not been fully studied. We aimed to assess differences in cardiotoxicity among cancer patients treated with different ADCs. Methods and Results An observational retrospective pharmacovigilance

T lymphocytes expressing the CD8 coreceptor, often referred to as cytotoxic T-lymphocytes (CTL), are critical in defending against virus infections and cancers. CD8 encompasses a diverse family of proteins, including homodimers, heterodimers, isoforms, and splice variants. CD8αβ heterodimers are the predominant form of the CD8 membrane protein, often anchored to lipid rafts to facilitate the activation

Hyperglycemia harms vascular health and promotes platelet aggregation. Reducing glucose concentration is crucial, and sugar alcohols may aid this effort. Used for over 50 years in food, cosmetic, and pharmaceutical industries, erythritol and xylitol minimally affect plasma glucose and insulin levels while promoting the release of beneficial gastrointestinal hormones such as e.g. glucagon-like peptide-1

Transcriptional regulation is essential for the development, homeostasis, and function of all organisms. Transcription factors and epigenetic modifiers play an indispensable role by direct or indirect interaction with DNA or chromatin. Although the role of transcription factor PRDM16 in adipose, hematopoietic, skeletal, and neural cell lineage specification is well-documented, its function within the

Aims Neointimal hyperplasia (NIH) characterized by vascular smooth muscle cell (VSMC) dysfunctions plays a critical role in many vascular diseases including atherosclerosis and restenosis, which leads to serious ischemic complications and has limited therapeutic approaches. Our previous studies confirm a critical role for nuclear factor erythroid 2-related factor 3 (Nrf3) in VSMC differentiation. However

Aims Thoracic aortic dissection (TAD) is a highly fatal disease lacking effective pharmacologic interventions in clinical practice. Emerging evidence indicates that the natriuretic peptide receptor C (NPR-C) plays a crucial role in the regulation of cardiovascular diseases. However, the precise involvement of NPR-C in TAD remains elusive. In this study, the role and molecular mechanisms of NPR-C in

Aims Molecular characterization of vulnerable atherosclerotic plaques often relies on transcriptomic data. However, RNA expression may not consistently align with protein expression. The proteomic landscape linked to plaque vulnerability is underexplored in human lesions. In this study, we analyzed a large mass spectrometry-based proteomics dataset from the plaque tissue of 320 patients to identify

Cardiovascular disease remains a persistent global health burden, underscoring the necessity for effective therapeutic strategies. Despite significant advances, the ability to mechanistically study human disease and predict clinical outcomes remains limited, especially in complex diseases such as heart failure. This limitation is evident through the continuous high attrition rates in drug development

Aims RNA interference therapies targeting liver expression of the gene proprotein convertase subtilisin/kexin type 9 (PCSK9) lower low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) levels. As opposed to monoclonal antibodies, which neutralise PCSK9 circulating protein, their effect on atherosclerotic cardiovascular disease (ASCVD) outcomes is unknown. We used genetic variants

Aims The prediction of atrial fibrillation (AF) progression and post-ablation recurrence is currently based on empirical estimates, leading to suboptimal predictive accuracy. This study investigates whether atrial remodelling, a key factor in the severity of atrial cardiomyopathy, could serve as a shared substrate influencing both AF progression and recurrence. We aimed to identify circular RNAs (circRNAs)

Aims Abdominal aortic aneurysm (AAA) treatment is upon a diameter threshold. Attempts for medical growth abrogation have failed thus far. This study aims to elucidate the heterogeneity of AAA histomorphology in correlation with individual patient and aneurysm metrics. Methods and results Samples from the left anterior aneurysm wall underwent histologic analysis including angiogenesis, calcification

Aims This study aims to resolve the mechanisms underlying Calmodulin (CaM)'s signaling diversity by investigating whether the three CaM genes—Calm1, Calm2, and Calm3—play distinct or redundant roles in cardiac myocytes, focusing on their spatial mRNA localization and interactions with key targets. Methods and Results We utilized single-molecule mRNA detection and 3D imaging to map the spatial distribution

Aims Circular RNA circSLC8a1 has been previously suggested to possess translation potential, but experimental evidence supporting this notion has been lacking. We aim to understand the functions of circSLC8a1 and its translated protein in cardiac remodeling. Methods and Results To elucidate the functional significance of circSLC8a1, we established a transgenic mouse line expressing circSLC8a1 and its

Aims Pulmonary hypertension (PH) is a common complication of left heart disease (LHD) that leads to right heart failure and death. Pulmonary artery (PA) stiffening has recently emerged as an important diagnostic and prognostic parameter in PH. The present study aimed to develop and validate an ultrasonographic index to identify PA stiffening in PH due to left heart disease (PH-LHD). Methods and Results

Aims Pronounced sex-differences are known in the incidence of atrial fibrillation (AF). In this study, we aimed to investigate the atrial electrophysiological properties that may underlie sex-differences in AF incidence in the younger population, focusing on IK1, a cardiac ion current important for action potential (AP) stability and triggered activity. Methods and Results We assessed sex-differences

Aim Polycystic kidney disease (PKD) patients have a high intracranial aneurysms (IAs) incidence and risk of rupture. The mechanisms that make PKD patients more vulnerable to IA disease are still not completely understood. The PCK rat is a well-known PKD model and has been extensively used to study cyst development and kidney damage. Here, we used this rat model to study IA induction and vulnerability

Aims Adult mammalian cardiomyocytes have limited regenerative potential, and after myocardial infarction (MI), injured cardiac tissue is replaced with fibrotic scar. In contrast, the neonatal mouse heart possesses a regenerative capacity governed by cardiomyocyte proliferation; however, a metabolic switch from glycolysis to fatty acid oxidation during postnatal development results in loss of this regenerative

Microplastics and nanoplastics are ubiquitous environmental pollutants that pose significant health risks. Several studies have reported the presence of these particles in various human tissues, including the heart, arterial plaques, and bloodstream of patients undergoing percutaneous coronary interventions. Emerging research suggests an association between these particles and an increased risk of

Aims The melanocortin receptor accessory protein 2 (MRAP2), which is abundantly expressed in the brain including the hypothalamus, has emerged as a key regulator of melanocortin-4 receptor (MC4R) activity. We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on autonomic and cardiovascular functions. Methods and Results Selective deletion of MRAP2

Heart failure with preserved ejection fraction (HFpEF) is a growing global health problem characterized by high morbidity and mortality, with limited effective therapies available. Obesity significantly influences haemodynamic and structural changes in the myocardium and vasculature, primarily through the accumulation and action of visceral adipose tissue. Particularly, epicardial adipose tissue (EAT)

Aims T cells contribute to hypertension; however, hypertension occurs in settings of T cell deficiency. Methods and results We studied two colonies of T/B cell-deficient RAG-1−/− mice with disparate responses to angiotensin II, being one protected from blood pressure increase and the other one responsive. This difference depends on the capability of hypertensive RAG-1−/− mice to expand natural killer

Aims The highly conserved long non-coding RNA (lncRNA) MIR505HG has been primarily recognized as a precursor for microRNAs (miR)-424 and miR-503. However, studies have since demonstrated that MIR503HG has distinct functions from its associated miRNAs, playing important roles in cell proliferation, invasion, apoptosis, and differentiation. While these miRNAs are known to influence cardiomyocyte differentiation

Aims Microvascular endothelial cells dysfunction can significantly worsen ischaemic stroke outcomes by disrupting tight junctions and increasing the acquisition of adhesion molecules, accelerating blood–brain barrier (BBB) disruption and pro-inflammatory response. The identification of drugs that improve endothelial cell function may be crucial for ischaemic stroke. It has been validated that empagliflozin

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 signaling is sufficient to suppress atherogenesis

Aim To investigate how psychosocial stress contributes to accelerated thrombosis, focusing on platelet activation and hyperreactivity. The specific objective was to identify novel platelet regulators involved in stress-mediated thrombosis, with a particular emphasis on the tetraspanin CD37. Methods and Results To explore how stress contributes to platelet hyperreactivity, platelets were isolated from

Aim Members of the VEGF family are crucial modulators of vascular and neural function. While VEGFA signaling has been shown to mitigate several aging-related cardiac phenotypes and prolong survival in aged mice, the role of VEGFB in cardiac aging remains underexplored. In this study, we identify a significant decline in Vegfb expression, particularly of its soluble isoform Vegfb186, in aged mouse and

Aims Replacement heart valves that grow with children remain an unmet need. We previously reported valves fabricated from tubes of fibroblast-derived collagenous matrix increased in size while functioning with low systolic gradients and less than moderate regurgitation over 52 weeks in most cases, when implanted as interpositional grafts in the pulmonary artery of lambs. Here, we evaluated valved conduits

Despite three decades of using statin therapy, 20 years of experience with ezetimbe, and availability of innovative non-statin lipid lowering therapies (LLT), there are still about 70% patients over the low-density lipoprotein cholesterol (LDL-C) goal, with every 5-6th being over the target from the group of very high and extremely high cardiovascular disease (CVD) risk patients. Adding another even

Aims Effective therapeutic drugs for calcific aortic valve disease (CAVD) are lacking, although its incidence has been increasing over the past decade, and is predicted to continue rising in the future. This study aimed to explore the role and potential mechanisms of liver X receptor α (LXRα) in CAVD, which offers a promising approach for treating CAVD. Methods and results Osteogenic stimulation was

As the population ages, the anticipated rates of dementia worldwide are likely to increase dramatically, especially in low- and middle-income countries; thus, any opportunity to modify dementia risk is especially critical. Hypertension is one risk factor that is highly prevalent, consistently important for late-life brain health, and which could represent a target for prevention of dementia. Furthermore

Animal models offer invaluable insights into disease mechanisms but cannot entirely mimic the variability and heterogeneity of human populations, nor the increasing prevalence of multi-morbidity. Consequently, employing human samples—such as whole blood or fractions, valvular and vascular tissues, myocardium, pericardium, or human-derived cells—is essential for enhancing the translational relevance

Aims Activation of the transcriptional factor Krüppel-like factor 5 (KLF5) is detrimental to chronic heart failure. We explored the involvement of KLF5 in myocardial ischemia/reperfusion injury. Methods and results Yorkshire pigs underwent 75΄ of ischemia, followed by 3h or 24h of reperfusion. C57BL/6J mice underwent 30΄ of ischemia, followed by 10’, 2h, 12h, 24h, or 4 weeks of reperfusion. Hearts

Background Alternative splicing of Titin (TTN) I-band exons produce protein isoforms with variable size and elasticity, but the mechanisms whereby TTN splice factors regulate exon usage and thereby determining cardiomyocyte passive stiffness and diastolic function, is not well understood. Non-coding RNA transcripts from the antisense strand of protein-coding genes have been shown to regulate alternative

Aims The potential of nanoparticles as effective drug delivery tools for treating failing hearts in heart failure remains a challenge. Leveraging the rapid infiltration of neutrophils into infarcted hearts after myocardial infarction (MI), we developed a nanoparticle platform engineered with neutrophil-membrane proteins for the targeted delivery of TAPI-1, a TACE/ADAM17 inhibitor, to the inflamed myocardium

Aims Abdominal aortic aneurysm (AAA) is a life-threatening condition where inflammation plays a key role. Currently, AAA treatment relies exclusively on surgical interventions, and no guideline drug therapy to prevent aneurysm growth or rupture is available. Pharmacological reprogramming of immune cell metabolism, through the modulation of the pyruvate dehydrogenase kinase/pyruvate dehydrogenase (PDK/PDH)