Heart failure (HF) is a life-threatening cardiovascular disease associated with high mortality, diminished quality of life, and a significant economic burden on both patients and society. The pathogenesis of HF is closely related to the endothelium, where endothelial ion channels play an important role in regulating intracellular Ca2+ signals. These ion channels are essential to maintain vascular function

Macrophage depletion exacerbates pressure overload-induced heart failure, but therapeutic translation is hindered by macrophage subset heterogeneity. The functional role of CD163+ macrophages in heart failure remains unclear. Transverse aortic constriction (TAC) was employed to induce pressure overload. Cd163−/− mice exhibited significantly aggravated TAC-induced left ventricular systolic dysfunction

Our previous work demonstrated that the DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) negatively affects post-infarct repair by promoting pro-inflammatory macrophages. However, whether cGAS and its downstream partner STING (Stimulator of Interferon Genes) regulate neutrophil production and function in the context of acute myocardial ischemia remains unclear. This study investigated the role of

Our prior research demonstrated that chronic intermittent hypobaric hypoxia (CIHH) pretreatment confers cardioprotection against ischemia/reperfusion (I/R) injury in rats. However, the precise mechanisms underlying CIHH’s cardioprotective effects remain insufficiently understood. This study aims to elucidate the upstream signaling pathways and dynamic regulation of BKCa channels in mediating CIHH-induced

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVD is known to increase the risk of subsequent neurodegeneration but the mechanism(s) and proteins involved have yet to be elucidated. We previously showed that myocardial infarction (MI), induced in mice and compared to sham-MI mice, leads to increases in protein aggregation, endoplasmic reticulum (ER) stress in both heart and

Individuals with heart failure have significantly reduced exercise capacity, a critical life-limiting symptom for those living with the disease. Heart failure is negatively correlated with decreased heart rate variability, including the loss of heart rate variability in tune with breathing—termed respiratory heart rate variability (RespHRV). We tested the hypothesis that restoration of RespHRV would

A major obstacle to progress in heart failure with preserved ejection fraction (HFpEF) is the paucity of clinically relevant animal models. We developed a large, translationally relevant model in Ossabaw minipigs, which are genetically predisposed to the metabolic syndrome (MetS). Pigs were fed a “Western diet” high in calories, fructose, fat, cholesterol, and salt and received 1–2 deoxy-corticosterone

The plasma membrane ATP-sensitive potassium (KATP) channel in cardiac myocytes plays a critical role in protecting the heart against ischemic injury. Post-translational modifications regulate KATP channel activity and play a role in cardioprotection. However, the role of tyrosine phosphorylation in KATP channel regulation remains unclear. In this study, we investigated the cardiac KATP channel subtype

Following myocardial infarction (MI), patients with type 2 diabetes mellitus (T2DM) have poorer prognosis which may be linked to increased susceptibility of coronary microvessels to injury. Interleukin-36 (IL-36) may mediate this injury but its role in the microcirculation of the chronically hyperglycaemic injured heart is unknown. Intravital and laser speckle imaging of the anaesthetised mouse beating

Myocardial infarction (MI) is a leading cause of heart failure, with thyroid hormone (TH) signaling playing a key role in heart function and postinfarct recovery. Despite evidence of TH administration's safety in cardiac patients, inconsistent therapeutic outcomes and limited understanding of its mechanisms hinder clinical translation. This study aims to investigate the long-term effect of acute triiodothyronine

Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover

The unsuccessful translation of cardiac regeneration and cardioprotection from animal experiments to clinical applications in humans has raised the question of whether microRNA bioinformatics can narrow the gap between animal and human research outputs. We reviewed the literature for the period between 2000 and 2024 and found 178 microRNAs involved in cardioprotection and cardiac regeneration. On analyzing

Intravenous thrombolysis remains the cornerstone for restoring cerebral reperfusion post-stroke. Despite recombinant tissue plasminogen activator (rtPA) achieving arterial reperfusion within 6 h, persistent microcirculatory blood flow reduction often hampers recovery. Exendin-4, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated potential for improving stroke outcomes, though its

Since cell dying in heart failure (HF) may vary based on the aetiology, we examined the main forms of regulated necrosis, such as necroptosis and pyroptosis, in the hearts damaged due to myocardial infarction (MI) or pressure overload. We also investigated the effects of a drug inhibiting RIP3, a proposed convergent point for both these necrosis-like cell death modes. In rat hearts, left ventricular

Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment

Myocarditis, an inflammatory disease of the heart muscle, is often triggered by viral infections. This inflammation, which can lead to severe cardiac dysfunction and adverse outcomes, is mediated by various CC and CXC chemokines that interact with receptors in a “one-to-many” fashion. Ticks have evolved chemokine-binding salivary proteins known as Evasins, which efficiently suppress inflammation. This

Studies on sex differences in myocardial infarction (MI) typically focus on males versus females, the exploration of hormonal physiologic variations and their impact on the infarct size remains limited. The objective of this study was to examine whether infarct size after myocardial ischemia/reperfusion injury in female rats differs in different phases of the estrous cycle, and according to the levels

Myocardial ischemia‒reperfusion (I/R) injury is the crucial cause of poor prognosis after revascularization in patients with myocardial infarction (MI) due to the lack of specific therapeutic drugs. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is related to the pathogenesis and progression of various cardiovascular diseases. However, the specific role of PCSK9 in I/R-induced cardiac injury

TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation in myocardial infarction and thereby attenuates inflammation. Motivated by the concept that heart failure with preserved ejection fraction (HFpEF) is a systemic inflammatory disease, we tested TY1 in a murine model of HFpEF. Intravenous TY1, packaged in a transfection

Novel biomarkers are needed to better identify—and distinguish—heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4+ T lymphocytes isolated from peripheral blood using

A long-standing aim in the setting of various pathologies including acute myocardial infarction, chronic kidney disease (CKD), and ischaemic stroke, has been to identify successful approaches to augment cellular and organ protection. Although the continual evolution and refinement of ideas over the past few decades has allowed the field to progress, we are yet to realise successful clinical translation

Cardiovascular disease and cancer are the leading causes of death in the Western world. The associated risk factors are increased by smoking, hypertension, diabetes, sedentary lifestyle, aging, unbalanced diet, and alcohol consumption. Therefore, the study of cellular metabolism has become of increasing importance, with current research focusing on the alterations and adjustments of the metabolism

Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain the cornerstones of oncological treatment. However, each carries a risk of cardiotoxicity, though the molecular mechanisms underlying these adverse effects differ. Common mechanisms

Ventricular fibrillation (VF)-induced cardiac arrest frequently complicates ST-segment elevation myocardial infarction (STEMI). Although larger infarct sizes (IS) correlate with a higher risk of VF, the influence of VF itself on IS has remained poorly investigated. To address this knowledge gap, we analyzed the effect of VF on IS in patients and two experimental models. From a prospective cohort, 30