Search Results (1,404)

Heart failure is a leading cause of global morbidity and mortality, often developing as a consequence of acute myocardial infarction. Current management focuses on timely reperfusion via percutaneous coronary intervention. Yet, this approach fails to prevent the molecular cascades that drive the death of viable yet stressed cardiomyocytes within the infarct and peri-infarct zone. Effective antifibrotic therapies remain limited, highlighting a critical gap in current management strategies. This review aims to integrate current understanding of the molecular mechanisms underpinning post-infarct fibrosis and potential interventions for therapeutic development. This emphasis on molecular death signal activation and cell elimination highlights the redundancy of interconnecting fibrosis pathways. Anti-inflammatory and cell-targeted therapies focussing on oxidative stress and haemodynamic load have demonstrated strong preclinical promise. Yet, these approaches have largely failed to translate into clinical benefit. Overall, these limitations emphasise a narrow therapeutic window for intervention. As such, current therapies often fail to preserve metabolically vulnerable myocardium that remains potentially salvageable. Therefore, emerging approaches including RNA-based therapies, cardiac reprogramming, and targeted delivery systems offer new opportunities to improve therapeutic precision. Collectively, these findings support a shift toward early, cell-targeted intervention strategies. This approach aims to prevent progression to heart failure and increases patient quality of life. Full article

Background/Objectives: Magnetic resonance imaging (MRI) provides a non-invasive means for a comprehensive assessment of the effect of radiation therapy (RT) on heart function. This study aims to determine RT induced cardiotoxicity in thoracic cancer patients using cardiac MRI. Methods: Cardiac MRI was performed at baseline and at six months post-treatment in patients undergoing standard-of-care RT for lung or esophageal cancers at a single institution. Parameters included regional myocardial strain in the longitudinal, circumferential, and radial directions as well as myocardium T1, T2, and extracellular-volume (ECV) maps. Cardiac segmental doses were extracted from the RT planning scans. The relationship between changes in segmental MRI parameters at six months and segmental heart RT dose were investigated. Results: Twelve patients underwent baseline MRI and four completed the follow-up MRI. Five of the segmental strain parameters showed notable changes between baseline and six-month follow-up. Increased doses in the heart base and apex were associated with moderate-to-large and mild deteriorations, respectively, in strain for all regions. Increased doses in the mid-ventricular regions were associated with improved strain in all regions. The segmental analysis revealed that myocardial regions nurtured by the left coronary artery are more negatively affected by radiation compared to those nurtured by the right coronary artery. Conclusions: Alterations in regional tissue and strain parameters on MRI vary according to local myocardial RT dose, suggesting there may be heterogeneity of radiation sensitivity for the heart substructures and regions. Changes in segmental strain parameters may reflect post-RT cardiac remodeling, but larger confirmatory studies are required. Full article

Heart failure (HF) and myocardial infarction (MI) are interconnected syndromes with overlapping pathogenic pathways, including ischemia, neurohormonal activation, and maladaptive remodeling. Hypoxia-response genes, lipid-handling genes, and extracellular matrix (ECM) genes each influence these processes. Understanding their integrated roles can uncover biomarkers and targets. A systematic literature search was conducted (PubMed, Web of Science, and Scopus; 2000–2026; English-only, following PRISMA guidelines) to identify studies on key genes in hypoxia signaling, lipid metabolism, and ECM remodeling in MI/HF. Acute hypoxia (via HIFs) orchestrates metabolic adaptation and inflammation, but chronic HIF activation drives fibrosis and dysfunction. In parallel, genes controlling triglyceride and cholesterol handling (e.g., LPL, APOC3) influence energy supply and vascular risk. Variants in these genes modulate plasma lipids and MI/HF risk. For example, genetic loss-of-function in APOC3 lowers triglycerides and reduces coronary risk. ECM-related genes (e.g., COL4A1, LRP1) govern fibrosis and vascular integrity. Mutations in COL4A1 cause cardiomyocyte hypertrophy and severe fibrosis, while LRP1 regulates matrix remodeling and is upregulated in ischemic myocardium. Throughout, gene functions span acute repair versus chronic maladaptation. Findings derive from mixed sources: rodent models and cell studies demonstrate mechanistic links, while human genetics and cohorts link gene variants to HF/MI outcomes. Many promising biomarkers (e.g., circulating ITGA1) are preliminary, lacking large prospective validation. Not all cited therapeutic ideas have been tested in the treatment of human cardiac disease. The literature mix of species, models, and patient cohorts introduces heterogeneity. Full article

Micro- and nanoplastics (MNPs) are ubiquitous environmental pollutants recognized as emerging and relevant risk factors for numerous human diseases, including cardiovascular diseases. MNPs enter the human body through ingestion, inhalation, and dermal penetration, and their toxicity varies according to size, shape, and chemical composition, most notably between microplastics (>1 µm) and nanoplastics (<1 µm), which differ in cellular uptake mechanisms and biodistribution. Recent evidence has confirmed their presence in cardiac and vascular tissues, raising significant concerns about their potential impact on human health. This review summarizes current knowledge on MNP exposure sources, physicochemical properties, and systemic bioavailability, with a particular emphasis on the mechanisms of transport that facilitate their deposition within the myocardium and vasculature. It further addresses a broad spectrum of cardiotoxic effects, including oxidative stress, mitochondrial injury, immune activation, ion channel disruption, cell death, and fibrosis. Endothelial dysfunction, vascular injury, and pro-atherogenic activity are also discussed. In addition to outlining existing detection techniques and emerging in vitro models, the review highlights initial steps toward the development of preventive strategies. Concluding with key knowledge gaps and future research directions, this article underscores the urgent need for standardized measurement tools, deeper insights into damage mechanisms, and clinical interventions to prevent MNP-induced cardiovascular diseases. Full article

Supplemental oxygen is a cornerstone intervention in modern clinical practice, widely used to correct hypoxemia in emergency, perioperative, and critical care settings. While oxygen therapy is lifesaving, accumulating evidence indicates that excessive oxygen exposure can induce significant pathophysiological disturbances, particularly within the cardiovascular and pulmonary systems. Hyperoxia (PaO₂ > 100 mm Hg) promotes the generation of reactive oxygen species (ROS), leading to oxidative stress, mitochondrial dysfunction, and the activation of pro-fibrotic pathways. When combined with mechanical ventilation, these effects are further amplified through alterations in intrathoracic pressure, reduced venous return, and increased pulmonary vascular resistance, collectively imposing hemodynamic stress on the myocardium. These mechanical and biochemical perturbations converge to drive structural, functional, and electrical remodeling of the heart, including conduction abnormalities and arrhythmogenesis. Emerging clinical insights, particularly from critically ill and COVID-19 populations, underscore the importance of titrated oxygen strategies that balance adequate tissue oxygenation with minimization of hyperoxic injury. This review synthesizes current evidence on hyperoxia-induced oxidative stress, heart-lung interactions, and mechanisms underlying myocardial remodeling to provide a comprehensive framework for optimizing oxygen therapy. Full article

Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) permits non-invasive quantification of myocardial fibrosis; however, automated scar segmentation remains challenging due to limited expert annotations and reduced image quality caused by acquisition noise and artefacts. We investigate two related questions: (i) whether inversion of a stochastic Gaussian diffusion process can reproduce the texture characteristics of low-signal-to-noise-ratio (SNR) LGE imaging, and (ii) whether the resulting synthetic data can improve automated fibrosis segmentation in annotation-limited settings. To this end, we introduce a mask-conditioned denoising diffusion probabilistic model (DDPM) that synthesises high-fidelity 2D short-axis LGE-CMR slices from three-class label maps (background, myocardium, scar), and we employ these synthetic images for training-set augmentation. The impact of augmentation was assessed using the nnU-Net v2 segmentation framework and benchmarked against exemplar-guided image synthesis with CoCosNet-v2 under identical data partitioning. On a held-out test set trained with 100 real cases, inclusion of 300 diffusion-generated cases increased the scar Dice coefficient from 0.173 to 0.271 (+56.7%), and the scar recall from 0.173 to 0.363, demonstrating enhanced sensitivity to fibrotic lesions. For comparable training budgets, diffusion-based augmentation consistently outperformed GAN-based augmentation, although performance improvements were non-monotonic with respect to the real-to-synthetic data ratio and attenuated as the size of the real dataset increased. A four-axis noise-fidelity analysis (spectral content, signal-dependent variance, short-range spatial correlation, distributional shape) further shows that the DDPM reproduces scanner-specific noise statistics substantially more faithfully than the GAN baseline, providing a mechanistic account for the augmentation gap. Full article

Mitochondrial reactive oxygen species (ROS) play a central role in cardiac ischemia/reperfusion injury, heart failure, and arrhythmogenesis, while also serving essential signaling functions under physiological conditions. Among the eleven identified mitochondrial ROS-producing sites, complexes I and III are considered the major contributors, particularly under conditions of impaired electron flow. However, much of the existing knowledge comes from rodent models or cultured cells and is often assumed to apply to humans. Here, ROS production from complexes I and III was measured directly in human myocardial and skeletal muscle biopsies and compared with corresponding rat tissues under identical experimental conditions. Hydrogen peroxide generation was quantified using Amplex UltraRed, with simultaneous monitoring of mitochondrial respiration using a Clark-type oxygen electrode. Across all examined mechanisms—reverse and forward electron transport at complex I and the ubiquinol oxidation site of complex III, rat tissues produced more ROS than human tissues, consistent with their higher respiratory rates. However, the dominant ROS-producing sites differed: in rats, complex III was the primary source, whereas in human tissues the highest ROS production occurred during reverse electron transport at complex I. When normalized to respiration, human tissues showed relatively greater ROS generation at complex I but markedly lower production at complex III. These direct measurements of mitochondrial ROS production in human myocardium provide new insight into cardiac redox physiology and may explain the limited clinical translation of cardioprotective strategies targeting mitochondrial ROS production, such as interventions aimed at modulating reperfusion injury or preconditioning. Full article

Mitochondria are vital organelles for human cells with fundamental roles in major metabolic processes such as calcium homeostasis, ATP production, apoptosis and signal transduction. Defective morphology and activity of these organelles have been tightly associated with the pathological onset of severe human disorders, including cardiovascular diseases. Targeting mitochondrial dysfunction has been an area of extensive research encompassing several approaches ranging from pharmacological agents to mitochondrial replacement techniques. Among them, mitochondrial transplantation has been a rapidly evolving approach, especially in the field of cardiovascular dysfunction for the restoration of injured or damaged myocardial cells. Various methods including tunneling nanotubes, nanoblade and “mitopunch” ensure the effective mitochondrial transfer from the donor to the recipient cell, with the internalization of the organelles, via endocytosis, enabling functional restoration. Results of preclinical and clinical trials involving mitochondrial transfer support the application of this technique in improving the function of the myocardium after damage caused by ischemia reperfusion injury. Herein, we discuss the beneficial role of mitochondrial transplantation in cardiovascular diseases and the current technical challenges of mitochondrial isolation, preservation, and targeted delivery, as well as their role in advancing precision medicine, offering a patient tailored therapeutic approach. Full article

Obesity and obstructive sleep apnea (OSA) frequently coexist and synergistically contribute to cardiovascular disease through interconnected mechanical, metabolic, and autonomic mechanisms. This interplay promotes myocardial electrical instability and structural remodeling, favoring the development and persistence of cardiac arrhythmias, particularly atrial fibrillation. Among the key mediators linking obesity to arrhythmogenesis, epicardial adipose tissue has emerged as a relevant factor that may contribute to local pro-inflammatory, pro-fibrotic, and autonomic effects on the myocardium. In parallel, OSA-related intermittent hypoxia and intrathoracic pressure swings further amplify electrical instability and autonomic imbalance, reinforcing a self-sustaining arrhythmogenic substrate. Therapeutic strategies are increasingly shifting toward upstream interventions targeting these underlying mechanisms. Metabolic therapies, including the dual GIP/GLP-1 receptor agonist tirzepatide, have demonstrated substantial weight reduction and improvement in OSA severity, with potential indirect benefits on arrhythmic risk through modulation of visceral adiposity, inflammation, and metabolic dysfunction. On the electrophysiological side, cardioneuroablation has emerged as a potentially investigational option in selected patients with vagally mediated bradyarrhythmias, although its role remains to be fully defined. Overall, these observations support an integrated, phenotype-driven approach combining respiratory therapy, metabolic modulation, and targeted electrophysiological interventions. This framework may help redefine therapeutic priorities, shifting from symptom control toward modification of the underlying arrhythmogenic substrate and improvement of long-term cardiovascular outcomes. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, and one of the key mechanisms driving the development of heart failure is pathological remodeling of the myocardium. This process involves complex structural, cellular, and metabolic alterations in which the immune system and its interactions with cardiomyocytes and fibroblasts play a central role. The aim of this work was to present the current state of knowledge on immunometabolism in cardiac remodeling and to discuss its pathophysiological relevance and therapeutic potential. This review focuses on the metabolism of cardiac macrophages, highlighting the differences between the pro-inflammatory (M1) and reparative (M2) phenotypes and their impact on inflammation, fibrosis, and myocardial regeneration. The roles of major metabolic pathways, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, are discussed, as well as the importance of the NLRP3 inflammasome and efferocytosis in regulating the inflammatory response. Furthermore, the review briefly incorporates recent insights into neutrophil, T cell, and regulatory T cell (Treg) metabolism and their contributions to inflammation, repair, and fibrotic remodeling. Particular attention is also given to cardiac fibroblasts and their metabolic reprogramming during fibrosis, with emphasis on the pivotal role of transforming growth factor-β (TGF-β) signaling. The review further discusses the role of microRNAs as mediators of intercellular communication integrating immunological and metabolic signals. The work is complemented by a discussion of therapeutic perspectives, including modulation of macrophage metabolism, fibrogenic signaling pathways, mitochondrial function, and miRNA-based therapies. Immunometabolism emerges as a promising research field whose further exploration may contribute to the development of novel, more precise strategies for the treatment of cardiovascular diseases. Full article

Acute myocardial infarction (AMI) causes high mortality, with cardiomyocyte apoptosis playing a critical role. Although circular RNAs modulate cardiac disorders, related mechanisms remain unclear. Here, we identify circRERE as a previously unrecognized pro-apoptotic regulator under ischemic stress. circRERE is markedly upregulated in ischemic myocardium and promotes apoptosis by sponging miR-27a-3p to elevate Caspase9. Using epigallocatechin gallate-primed exosomes (EGCG-primed exosomes, Exo^EGCG) as a tool to modulate circRERE, we found that Exo^EGCG significantly reduced circRERE levels, restored miR-27a-3p activity, and suppressed Caspase9. Gain- and loss-of-function tests confirmed that circRERE mediates Exo^EGCG-derived protection. Collectively, circRERE represents a novel and actionable target for AMI, with Exo^EGCG serving as an effective delivery platform. Full article

Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and epigenetic remodeling in the placenta and fetal tissues. These molecular alterations impair placental lipid transport and nutrient sensing, leading to hypertrophy of fetal liver, myocardium, and adipose tissue, while disrupting neonatal glucose and lipid homeostasis and increasing susceptibility to perinatal complications and long-term metabolic disorders. This review aims to evaluate mechanistic pathways linking maternal lipid metabolism, oxidative stress, placental function, and fetal organ remodeling. Mechanistic and translational studies were identified through searches of PubMed, Scopus, the Cochrane Library, and Web of Science (2000–2025) using predefined keywords including lipid metabolism, free fatty acids, oxidative stress, placental lipid transport, epigenetics, DNA methylation, fetal programming, and perinatal outcomes. Evidence indicates that maternal lipid imbalance drives placental oxidative and epigenetic modifications, directly contributing to fetal organ hypertrophy and neonatal metabolic dysregulation. In conclusion, maternal dyslipidemia represents a modifiable determinant of fetal organ hypertrophy and long-term metabolic risk, supporting the clinical relevance of maternal lipid monitoring and targeted metabolic interventions during pregnancy. Full article

Feline hepatic lipidosis (FHL) is a life-threatening, common hepatobiliary disease characterized by massive triglyceride accumulation in the liver, often triggered by anorexia and negative energy balance in cats. This condition causes severe metabolic stress that may secondarily impact myocardial integrity. This observational clinical study evaluated serum homocysteine (Hcy) and high-sensitivity cardiac troponins (hs-cTnI, hs-cTnT) to assess secondary myocardial injury and their prognostic value in FHL. Fifty cats, comprising 30 with naturally occurring FHL and 20 healthy controls, were included. Serum Hcy, hs-cTnI, and hs-cTnT concentrations were measured using feline-specific ELISA kits, and routine biochemical parameters, alongside hospitalization times, were recorded. Results indicated that Hcy, total bilirubin, and liver enzymes were significantly elevated in the FHL group compared to controls (p < 0.001). However, hs-cTnI and hs-cTnT levels did not differ significantly between the groups. Notably, Hcy exhibited a strong positive correlation with hospitalization time (r = 0.89, p < 0.001). The absence of significant hs-cTn elevations suggests the feline myocardium remains largely resistant to acute necrosis during FHL. Nevertheless, relative hyperhomocysteinemia is a powerful prognostic biomarker for prolonged hospitalization in affected cats. Full article

Background/Objectives: Myocardial ischemia–reperfusion injury (MIRI) remains an ever-growing threat in the field of cardiology, as it has become a major risk factor for unfavorable outcomes following reperfusion therapies. Oxidative stress and inflammation remain the key pathophysiological mechanisms underlying MIRI, and the presently available treatments fail to prevent this process effectively. This systematic review aimed to summarize and critically assess the latest preclinical research (2020–2026) on nanocarrier-based interventions targeting oxidative stress in MIRI, highlighting the potential of the new nanostructures in cardioprotection. Methods: A total of 24 studies meeting the PRISMA criteria have been found through a literature search of PubMed, Embase, and Web of Science databases published between 2020 and 2026. The studies eligible for inclusion had focused on the efficacy of nanocarrier-based interventions in preclinical studies of MIRI. Results: Of the 24 included studies, all investigated nanocarrier-based interventions in preclinical models of MIRI. In vitro, ex vivo, and in vivo models were diverse, with most studies being a combination of both in vitro and in vivo models. Commonly studied were lipid-based nanocarriers, polymeric nanoparticles, and biomimetic nanocarriers. Across studies assessed for this review, treatments with nanocarriers were seen to suppress inflammatory and oxidative stress pathways, with a few studies showing a suppression of cardiomyocyte apoptosis. Cardiac function was restored as determined by echocardiography analyses or ex vivo models of the myocardium, thus validating that the nanocarrier-mediated therapies are effective against MIRI. Conclusions: The analyzed preclinical studies indicate that the described therapies could provide a promising basis for future clinical trials in the treatment of MIRI, provided their safety and efficacy are confirmed in clinical trials. Full article

Background/Objective: Cardiac innervation plays a critical role in regulating myocardial function and enabling the heart to adapt to physiological and pathological conditions. Although the general features of sympathetic and parasympathetic innervation of the myocardium are well described, the spatial organisation of nerve fibres within the cardiac muscle remains incompletely characterised. This study aimed to develop and validate the SKUF (Slice–Keep–Unwrap–Fuse) protocol, a multimodal framework for mapping myocardial innervation through the integration of histological data and magnetic resonance imaging (MRI). Methods: The study was performed on the heart of a 7-year-old patient who died from rupture of a cerebral vascular malformation without evidence of cardiovascular disease. Prior to histological processing, post-mortem MRI was performed to provide a precise anatomical reference. The heart was sectioned into sequential transverse rings of 4 mm thickness, yielding 71 paraffin blocks. Histological sections (3 μm) were immunostained with antibodies against UCHL-1 to visualise nerve fibres and scanned using an Aperio AT2 system (20× magnification). Automated image analysis was conducted using the SVSSlide Processor module, which included tissue segmentation, colour-based nerve fibre detection, and sliding-window density mapping. Heatmaps were assembled into ring-based myocardial reconstructions and co-registered with MRI slices using combined rigid and deformable registration, followed by three-dimensional reconstruction of innervation patterns. Results: A higher density of nerve fibres was observed in the right ventricular myocardium compared with the left ventricle, whereas larger nerve trunks were identified in the epicardium of the left ventricle. Quantitative analysis revealed a pronounced longitudinal gradient of innervation, with minimal density in the apical region and progressive increases towards the mid-ventricular segments, where maximal density and spatial organisation of neural structures were observed. The atrioventricular groove exhibited the greatest heterogeneity of innervation due to the presence of large nerve trunks and ganglionated plexuses. Integration of histological maps with MRI enabled three-dimensional visualisation of spatial clusters of nerve fibres. Conclusions: The SKUF protocol provides a robust framework for integrating histological and MRI data to generate three-dimensional maps of myocardial innervation. This approach may facilitate the development of high-resolution anatomical atlases of cardiac innervation and support future studies of neurocardiac mechanisms of arrhythmogenesis and targeted neuromodulation. Full article