Search Results (130)

Background/Objectives: Blunt cardiac injury (BCI) is a severe medical condition that may arise as a result of various traumas, including motor vehicle accidents and falls. The main objective of this study was to explore the role and underlying mechanisms of the TRPV4 gene in BCI. Elucidating the function of TRPV4 in BCI may reveal potential novel therapeutic targets for the treatment of this condition. Methods: Rats in each group, including the SD control group (SDCON), the SD blunt-trauma group (SDBT), the TRPV4 gene-knockout control group (KOCON), and the TRPV4 gene-knockout blunt-trauma group (KOBT), were all freely dropped from a fixed height with a weight of 200 g and struck in the left chest with a certain energy, causing BCI. After the experiment, the levels of serum IL-6 and IL-1β were detected to evaluate the inflammatory response. The myocardial tissue structure was observed by HE staining. In addition, cardiac transcriptome analysis was conducted to identify differentially expressed genes, and metabolomics studies were carried out using UHPLC-Q-TOF/MS technology to analyze metabolites. The results of transcriptomics and metabolomics were verified by qRT-PCR and Western blot analysis. Results: Compared with the SDCON group, the levels of serum IL-6 and IL-1β in the SDBT group were significantly increased (p < 0.001), while the levels of serum IL-6 and IL-1β in the KOBT group were significantly decreased (p < 0.001), indicating that the deletion of the TRPV4 gene alleviated the inflammation induced by BCI. HE staining showed that myocardial tissue injury was severe in the SDBT group, while myocardial tissue structure abnormalities were mild in the KOBT group. Transcriptome analysis revealed that there were 1045 upregulated genes and 643 downregulated genes in the KOBT group. These genes were enriched in pathways related to inflammation, apoptosis, and tissue repair, such as p53, apoptosis, AMPK, PPAR, and other signaling pathways. Metabolomics studies have found that TRPV4 regulates nucleotide metabolism, amino-acid metabolism, biotin metabolism, arginine and proline metabolism, pentose phosphate pathway, fructose and mannose metabolism, etc., in myocardial tissue. The combined analysis of metabolic and transcriptional data reveals that tryptophan metabolism and the protein digestion and absorption pathway may be the key mechanisms. The qRT-PCR results corroborated the expression of key genes identified in the transcriptome sequencing, while Western blot analysis validated the protein expression levels of pivotal regulators within the p53 and AMPK signaling pathways. Conclusions: Overall, the deletion of the TRPV4 gene effectively alleviates cardiac injury by reducing inflammation and tissue damage. These findings suggest that TRPV4 may become a new therapeutic target for BCI, providing new insights for future therapeutic strategies. Full article

Background: The early repolarization pattern (ERP) on electrocardiography (ECG) has been associated with an increased risk of ventricular arrhythmias in susceptible individuals. This study aimed to evaluate the impact of exercise on echocardiographic parameters to explore the potential influence of ERP on hemodynamic response. Methods: Twenty-five healthy, young males with ERP (ERP+ group) and 25 age-matched healthy males without ERP (ERP− group) were enrolled. Comprehensive transthoracic echocardiography was performed at rest and during the early recovery phase following a treadmill exercise test. Baseline values and exercise-induced changes in both conventional and strain-derived echocardiographic parameters were analyzed and compared between groups. Results: Anthropometric measures and resting vital signs were similar in both groups. At baseline, the ERP+ group had a shorter QRS duration. Both groups demonstrated excellent cardiovascular fitness, with comparable chronotropic and pressor responses to exercise. Resting and early recovery-phase echocardiographic parameters were largely similar between ERP+ and ERP− individuals, with no overt structural or functional abnormalities observed in either group. However, ERP+ individuals showed significantly greater reductions in left ventricular end-diastolic volume and stroke volume following exercise, suggesting a distinct volumetric response to physical stress. Conclusions: ERP in healthy young males is not associated with structural cardiac abnormalities or overt myocardial dysfunction. The observed exercise-induced volumetric changes may indicate subtle differences in hemodynamic adaptation, warranting further investigation. Full article

Cardiopulmonary exercise testing combined with exercise stress Echocardiography (CPET-ESE) is an advanced diagnostic modality for evaluating cardiovascular disease and tailoring patient-specific treatment strategies. By integrating metabolic, ventilatory, and hemodynamic data with real-time imaging, CPET-ESE offers a comprehensive assessment of cardiovascular function under physiological stress. CPET provides detailed insights into metabolic and ventilatory performance, while ESE allows for the dynamic visualisation of cardiac structure and function during exercise. This review outlines the physiological foundations and core parameters of CPET and ESE, emphasising their complementary roles in cardiovascular diagnostics and prognostication and exploring their clinical value for evaluating unexplained dyspnoea and exercise-induced hemodynamic abnormalities. CPET-ESE plays a pivotal role in detecting subtle hemodynamic abnormalities, assessing functional capacity, and contributing to earlier diagnosis, targeted interventions, and improved clinical outcomes. Full article

Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60 mg/Kg). Aerobic training consisted of 30 min treadmill running at ~55% of maximal capacity, 5×/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA-seq analysis was performed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs. Enrichment pathways analyses and weighted gene co-expression network analysis (WGCNA) identified potential key genes involved in disrupted lipid metabolism in sedentary cachectic rats, which were not observed in the exercised cachectic rats. Validation of DEGs related to lipid metabolism confirmed that Dgat2 gene expression was modulated by aerobic training in CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid metabolism in rats with CC, highlighting its therapeutic potential. Full article

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. Full article

Significant challenges persist in diagnosing non-ischemic cardiomyopathies (NICMs) owing to early morphological overlap and subtle functional changes. While cardiac magnetic resonance (CMR) offers gold-standard structural assessment, current morphology-based AI models frequently overlook key biomechanical dysfunctions like diastolic/systolic abnormalities. To address this, we propose a dual-path hybrid deep learning framework based on CNN-LSTM and MLP, integrating anatomical features from cine CMR with biomechanical markers derived from intraventricular pressure gradients (IVPGs), significantly enhancing NICM subtype classification by capturing subtle biomechanical dysfunctions overlooked by traditional morphological models. Our dual-path architecture combines a CNN-LSTM encoder for cine CMR analysis and an MLP encoder for IVPG time-series data, followed by feature fusion and dense classification layers. Trained on a multicenter dataset of 1196 patients and externally validated on 137 patients from a distinct institution, the model achieved a superior performance (internal AUC: 0.974; external AUC: 0.962), outperforming ResNet50, VGG16, and radiomics-based SVM. Ablation studies confirmed IVPGs’ significant contribution, while gradient saliency and gradient-weighted class activation mapping (Grad-CAM) visualizations proved the model pays attention to physiologically relevant cardiac regions and phases. The framework maintained robust generalizability across imaging protocols and institutions with minimal performance degradation. By synergizing biomechanical insights with deep learning, our approach offers an interpretable, data-efficient solution for early NICM detection and subtype differentiation, holding strong translational potential for clinical practice. Full article

Albumin is the most abundant protein synthesized exclusively by the hepatocytes in the liver. Once secreted into plasma, it helps in the maintenance of osmotic pressure, as well as the exertion of defensive roles such as anti-oxidative and anti-inflammatory functions. Dysregulation in the synthesis and clearance of albumin is observed in various hepatic and extra-hepatic diseases. Abnormal levels of albumin could be either a cause or an effect of various pathological ailments, including hepatic, cardiac, renal, neurological, etc. Owing to its long half-life and multiple binding sites in its heart-shaped structure, it interacts with various internal agents, such as hormones, or external substances like drugs, which is why transportation can be one of its many functions. Additionally, albumin’s drug interactions, as well as displacement of albumin–drug binding, could have serious clinical consequences, and careful considerations should be made in determining an appropriate drug regimen to achieve a desired therapeutic outcome with minimal side effects. Moreover, albumin also undergoes several post-translational modifications that can influence its physiological roles, including drug binding and antioxidant functions. Furthermore, it has a complicated role in physiology, where it can help in maintaining plasma oncotic pressure and prevent endothelial cell apoptosis but can have adverse effects on the lungs and kidneys. These adverse effects are mainly attributed to ER stress and inflammasome activation. This narrative review provides an overview of the general biology of albumin and its effects in physiology, with a focus on its beneficial and adverse effects and the underlying molecular mechanisms. Full article

Myocardial infarction (MI) is a leading cause of morbidity worldwide, resulting from ischemic damage and necrosis to cardiomyocytes. While the standard treatment regimen for MI can be successful in restoring coronary perfusion, it typically does not resolve myocardial damage, which can leave patients particularly vulnerable to complications such as heart failure or electrical conduction abnormalities. Stem cell therapies offer a promising novel approach aimed at restoring cardiac function and decreasing the incidence of functional complications after an MI. This review used a literature search to evaluate the current landscape of stem cell therapy for post-MI recovery and focuses on the stem cell candidates for MI recovery therapy, delivery methods of such treatment, and their effectiveness. Both preclinical and clinical trials have demonstrated the safety of stem cells, but have struggled with limited cell retention, inconsistent efficacy, and survival. Mechanisms are employed by stem cells to promote regeneration, such as paracrine signaling, angiogenesis, and structural remodeling, in addition to the various stem cell delivery methods, including intracoronary infusion, direct myocardial injection, and intravenous administration. Furthermore, some strategies to combat past challenges in this field are discussed; for instance, extracellular vesicles, bioengineered patches, hydrogels, gene editing, and bioprinting. This article will provide a framework for future research in stem cell therapies and highlight the current progress in the field. Full article

Background and Objectives: Nonischemic cardiomyopathies comprise a wide spectrum of heart muscle disorders characterized by different morphological, functional, and tissue abnormalities. Cardiovascular magnetic resonance (CMR) represents the gold standard imaging modality for assessing cardiac morphology, systolic function, and tissue characterization, thereby aiding in early diagnosis, precise phenotyping, and tailored treatment. The aim of this review is to provide an up-to-date overview of CMR techniques for studying myocardial perfusion and their applications to nonischemic cardiomyopathy, not only to rule out an underlying ischemic aetiology but also to investigate the pathophysiological characteristics of microcirculatory dysfunction in these patients. Materials and Methods: We performed a structured review of the literature focusing on first-pass gadolinium perfusion sequences, stress protocols, and emerging pixel-wise perfusion mapping approaches. Studies were selected to illustrate the methods for image acquisition, post-processing, and quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), as well as to highlight associations with clinical endpoints. Results: First-pass CMR perfusion imaging reliably detects diffuse and regional microvascular dysfunction across cardiomyopathies. Semi-quantitative parameters (e.g., upslope, MPRI) and quantitative MBF mapping (mL/g/min) have demonstrated that impaired perfusion correlates with disease severity, extent of fibrosis, and adverse outcomes, including heart failure hospitalization, arrhythmias, and mortality. Novel automated pixel-wise mapping enhances reproducibility and diagnostic accuracy, distinguishing coronary microvascular dysfunction from balanced three-vessel disease. Microvascular dysfunction—present in approximately 50–60% of dilated cardiomyopathy (DCM), 40–80% of hypertrophic cardiomyopathy (HCM), and >95% of cardiac amyloidosis (CA) patients—has emerged as a key driver of adverse outcomes. Perfusion defects appear early, often preceding overt hypertrophy or fibrosis, and provide incremental prognostic value beyond conventional CMR metrics. Conclusions: CMR represents a powerful tool for detecting myocardial perfusion abnormalities in nonischemic cardiomyopathies, improving phenotyping, risk stratification, and personalized management. Further standardization of quantitative perfusion techniques will facilitate broader clinical adoption. Full article

Type 2 diabetes is a significant risk factor for cardiovascular disease, particularly coronary heart disease, heart failure, and diabetic cardiomyopathy. Diabetic cardiomyopathy, characterized by heart dysfunction in the absence of coronary artery disease or hypertension, is triggered by various mechanisms, including hyperinsulinemia, insulin resistance, and inflammation. At the cellular level, increased insulin resistance leads to an imbalance in lipid and glucose metabolism, causing oxidative stress, mitochondrial dysfunction, and excess production of reactive oxygen species (ROS). This disrupts normal heart function, leading to fibrosis, hypertrophy, and cardiac remodeling. In diabetic patients, the excessive accumulation of fatty acids, advanced glycation end products (AGEs), and other metabolic disturbances further contribute to endothelial dysfunction and inflammatory responses. This inflammatory environment promotes structural damage, apoptosis, and calcium-handling abnormalities, resulting in heart failure. Additionally, diabetes increases the risk of arrhythmias, such as atrial fibrillation, which worsens cardiac outcomes. New insights into these molecular mechanisms have led to improvements in diabetes management, focusing on mitigating complications and understanding the cellular processes involved. Recent therapeutic advances, such as SGLT-2 inhibitors, have shown promise in addressing the energy imbalance and cardiac dysfunction seen in diabetic cardiomyopathy, offering new hope for better cardiovascular outcomes. Full article

Cardiomyopathies comprise a heterogeneous group of cardiac disorders characterized by structural and functional abnormalities in the absence of significant coronary artery disease, hypertension, valvular disease, or congenital defects. Major subtypes include hypertrophic, dilated, arrhythmogenic, and stress-induced cardiomyopathies. Oxidative stress (OS), resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, has emerged as a key contributor to the pathogenesis of these conditions. ROS-mediated injury drives inflammation, protease activation, mitochondrial dysfunction, and cardiomyocyte damage, thereby promoting cardiac remodeling and functional decline. Although numerous studies implicate OS in cardiomyopathy progression, the precise molecular mechanisms remain incompletely defined. This review provides an updated synthesis of current findings on OS-related signaling pathways across cardiomyopathy subtypes, emphasizing emerging therapeutic targets within redox-regulatory networks. A deeper understanding of these mechanisms may guide the development of targeted antioxidant strategies to improve clinical outcomes in affected patients. Full article

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder marked by abnormal thickening of the left ventricular myocardium, often leading to arrhythmias and heart failure. Mutations in sarcomeric protein genes, particularly MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), are major contributors to HCM pathogenesis. This study aims to investigate the structural and functional effects of two HCM-associated missense mutations, p.S236G and p.E334K, located within the C0–C2 domains of cMyBP-C. Methods: Following in silico analysis, a bacterial expression system was applied, enabling the discrete C0–C2 domains of wild-type (cMyBP-C^WT) and mutant (cMyBP-C^S236G and cMyBP-C^E334K) cMyBP-C proteins to be expressed and purified as recombinant proteins. Structural and stability changes were assessed using circular dichroism (CD), differential scanning calorimetry (DSC), and chemical denaturation assays. Functional impact on actin binding was also evaluated in vitro. Results: CD analysis revealed altered secondary structure in both mutants compared to the wild-type protein. Thermal and chemical stability assays indicated increased stability in the cMyBP-C^E334K mutant, suggesting that it exhibits a more rigid conformation. This increased rigidity corresponded with a significant reduction in the actin-binding affinity relative to the wild-type protein. Conclusions: Our findings demonstrate specific detrimental effects of the p.E334K mutation and underscore the importance of understanding the structural and functional consequences of HCM-associated mutations to assist the development of targeted therapeutic strategies. Full article

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, representing a complex clinical syndrome in which the heart’s ability to pump blood efficiently is impaired. HF can be subclassified into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), each with distinct pathophysiological mechanisms and varying levels of severity. The progression of HF is significantly driven by cardiac fibrosis, a pathological process in which the extracellular matrix undergoes abnormal and uncontrolled remodelling. Cardiac fibrosis is characterized by excessive matrix protein deposition and the activation of myofibroblasts, increasing the stiffness of the heart, thus disrupting its normal structure and function and promoting lethal arrythmia. MicroRNAs, long non-coding RNAs, and circular RNAs, collectively known as non-coding RNAs (ncRNAs), have recently gained significant attention due to a growing body of evidence suggesting their involvement in cardiac remodelling such as fibrosis. ncRNAs can be found in the peripheral blood, indicating their potential as biomarkers for assessing HF severity. In this review, we critically examine recent advancements and findings related to the use of ncRNAs as biomarkers of HF and discuss their implication in fibrosis development. Full article

Background: Chronic liver disease (CLD) and cirrhosis contribute to approximately 2 million deaths annually, with primary causes including alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and chronic hepatitis B and C infections. Among these, MASLD has emerged as a significant global health concern, closely linked to metabolic disorders and a leading cause of liver failure and transplantation. Objective: This review aims to highlight the interplay between cirrhosis and cardiac dysfunction, emphasizing the pathophysiology, diagnostic criteria, and management of cirrhotic cardiomyopathy (CCM). Methods: A comprehensive literature review was conducted to evaluate the hemodynamic and structural cardiac alterations in cirrhosis. Results: Cirrhosis leads to portal hypertension and systemic inflammation, contributing to CCM, which manifests as subclinical cardiac dysfunction, impaired contractility, and electrophysiological abnormalities. Structural changes, such as increased left ventricular mass, myocardial fibrosis, and ion channel dysfunction, further impair cardiac function. Vasodilation in the splanchnic circulation reduces peripheral resistance, triggering compensatory tachycardia, while the activation of the renin–angiotensin–aldosterone system (RAAS) promotes fluid retention and increases cardiac preload. Chronic inflammation and endotoxemia exacerbate myocardial dysfunction. The 2005 World Congress of Gastroenterology (WCG) and the 2019 Cirrhotic Cardiomyopathy Consortium (CCC) criteria provide updated diagnostic frameworks that incorporate global longitudinal strain (GLS) and tissue Doppler imaging (TDI). Prolonged QT intervals and arrhythmias are frequently observed. Managing heart failure in cirrhotic patients remains complex due to intolerance to afterload-reducing agents, and beta-blockers require careful use due to potential systemic hypotension. The interaction between CCM and major interventions, such as transjugular intrahepatic portosystemic shunt (TIPS) and orthotopic liver transplantation (OLT), highlights the critical need for thorough preoperative cardiac evaluation and vigilant postoperative monitoring. Conclusions: CCM is a frequently underdiagnosed yet significant complication of cirrhosis, impacting prognosis, particularly post-liver transplantation. Early identification using echocardiography and thorough evaluations of arrhythmia risk in cirrhotic patients are critical for optimizing management strategies. Future research should focus on targeted therapeutic approaches to mitigate the cardiac burden in cirrhotic patients and improve clinical outcomes. Full article

Coronary microvascular dysfunction (CMD) is characterized by structural and functional abnormalities in the coronary microvasculature which can lead to ischaemia and angina and is increasingly recognized as a major contributor to adverse cardiovascular outcomes. Despite its clinical importance, the diagnosis of CMD remains limited compared with traditional atherosclerotic coronary artery disease. Furthermore, the historical lack of non-invasive methods for detecting and quantifying CMD has hindered progress in understanding its pathophysiology and clinical implications. This review explores advancements in non-invasive cardiac imaging that have enabled the detection and quantification of CMD. It evaluates the clinical utility, strengths and limitation of these imaging modalities in diagnosing and managing CMD. Having improved our understanding of CMD pathophysiology, cardiac imaging can provide insights into its prognosis and enhance diagnostic accuracy. Continued innovation in imaging technologies is essential for advancing knowledge about CMD, leading to improved cardiovascular outcomes and patient care. Full article