Journal of Cardiovascular Translational Research最新文献

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, necessitating innovative therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as regulators of gene expression, influencing various cellular processes involved in cardiovascular health and disease. This review explores the functional roles of lncRNAs in CVD pathogenesis, highlighting their involvement in processes such as hypertrophy, fibrosis, inflammation, and vascular remodeling. We discuss their potential as diagnostic biomarkers and therapeutic targets, alongside recent advancements in gene therapy approaches. While no lncRNA-based therapies have yet reached clinical trials, emerging RNA-targeting technologies, including antisense oligonucleotides, siRNAs, and CRISPR-based interventions, offer promising avenues for future therapeutic applications. Additionally, we examine the challenges associated with delivering lncRNA-based therapies, evaluating both viral and non-viral delivery methods, and their potential to revolutionize cardiovascular medicine. Ultimately, a deeper understanding of lncRNA biology and improvements in delivery strategies will be crucial in translating these findings into clinical treatments.

The article presents the results of applying artificial intelligence algorithms to analyze multichannel electrograms of bioelectrical activity registered by microelectrode arrays from myocardium of isolated rat hearts under the influence of L-carnitine and adrenaline. Localization of activation times on electrograms was performed using a new neural network model based on the U-Net architecture adapted for one-dimensional signal segmentation. In the organism, L-carnitine is necessary for the oxidation of fatty acids. But the effects of its supplemental intake on the cardiovascular system are still poorly understood. A decrease in heart rate, myocardial excitation conduction velocity, intensity of coronary blood flow and physiologic cardiac response to adrenaline action ex vivo caused by L-carnitine were shown. The methodological approach, applying a neural network to analyze data from microelectrode arrays, tested in this research can be translated into clinical practice for electrograms obtained by electrophysiology study of human heart.

Vascular endothelial growth factor receptor 1 (VEGFR1) is a key regulator of endothelial function, angiogenesis, inflammation, and cardiomyocyte survival, with both beneficial and deleterious effects in cardiovascular disease. In this review, we provide some key information on the molecular biology governing VEGFR1 function, its role in cardiovascular diseases and describe gene therapy strategies targeting either membrane-bound or its soluble isoform sFLT1 to treat these diseases. Clinical Relevance Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Thus, new therapeutic targets and strategies are warranted to mitigate CVDs economic and societal burdens. Members of the Vascular Endothelial Growth Factor (VEGF) family and their receptors stand as key players in the majority of biological processes underlying CVDs, including inflammation, angiogenesis, and cardiomyocyte function. This review focuses on the role of VEGFR1 in the onset and progression of the most common CVDs, with particular emphasis on the signaling mechanisms occurring in different cell types, and discusses its potential as a target for gene therapy.

Investigated the role and possible mechanisms of SMILR in angiogenesis among chronic heart failure (CHF) patients to establish novel biomarkers for the clinical assessment of CHF. qPCR was employed to assess the levels of serum SMILR and miR-10b-3p. ROC analysis and logistic regression were utilized to evaluate the diagnostic and predictive value of SMILR. Pearson correlation analysis was conducted to explore the relationship between serum SMILR and myocardial injury markers, as well as cardiac function indicators. In CHF patients, serum SMILR was up-regulated, while miR-10b-3p was down-regulated. In a hypoxic injury model, SMILR silencing restored both the function and oxidative stress levels of hCMECs, and promoted the secretion of pro-angiogenic factors. Inhibition of miR-10b-3p prevented the angiogenic enhancement associated with the knockdown of SMILR. SMILR influences angiogenesis and CHF progression via miR-10b-3p. SMILR is a promising candidate for early detection and subsequent therapy in CHF.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes, characterized by myocardial injury, fibrosis, and heart dysfunction. The pathogenesis remains poorly understood, with limited treatment options. Recent research highlights the roles of regulated cell death (RCD) and inflammation in DCM progression. RCD types, including apoptosis, pyroptosis, ferroptosis, and necroptosis, are central to myocardial damage and are closely linked to oxidative stress and inflammation. Inflammatory pathways like NLRP3, NF-κB, and TLR4 activate cytokines (TNF-α, IL-1β, IL-6), exacerbating fibrosis and heart failure. Notably, RCD and inflammation create a feedback loop, amplifying each other and accelerating DCM. This review explores the interactions between RCD and inflammatory signaling, their contribution to myocardial injury, and potential therapeutic strategies targeting both pathways. A multi-targeted approach to DCM therapy may offer new avenues for treatment.

Inherited cardiac arrhythmias are genetic disorders that impact the heart's electrical circuitry. These disorders are caused by inherited mutations and markedly increase the mortality risk of affected individuals. Conventional treatments, such as pharmacological agents for rate and rhythm control or surgical interventions, are often not efficacious and cause long-term complications. Gene therapy has recently emerged as a feasible and potentially curative approach for treating inherited cardiac arrhythmia syndromes. Advancements in elucidating the molecular mechanisms, pinpointing essential candidate genes, and improving gene delivery have rendered gene therapy as a feasible treatment alternative. This review examines recent studies on gene therapy applications in Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, familial atrial fibrillation, and arrhythmogenic cardiomyopathy. Additionally, we analyze current advancements in viral and non-viral gene delivery methods, highlighting their therapeutic potential and related challenges.

Individuals with severe obesity (SO) are at a high risk of developing cardiovascular disease, but traditional lipid parameters are insufficient for accurately assessing the risk. This study aims to investigate the advanced characteristics of lipoproteins that may contribute to subclinical atherosclerosis in SO and the impact of bariatric surgery (BS). The study included 37 patients with SO with a one-year follow-up post-BS, and 40 control subjects. Advanced lipoprotein profiles were assessed using nuclear magnetic resonance. BS normalized proatherogenic lipoprotein alterations in SO. Small LDL and medium HDL particle numbers differed between plaque and non-plaque groups. A ratio of these particles showed an AUC of 83%, suggesting it could effectively predict subclinical atherosclerosis. Advanced NMR analysis offers more specific information on lipid profiles in SO. The small LDL-P to medium HDL-P ratio could be a valuable tool for detecting and managing subclinical atherosclerosis in this population.

Recent research shows exercise is good for heart health, emphasizing the importance of physical activity. Sedentary behavior increases the risk of cardiovascular disease, while exercise can help prevent and treat it. Additionally, physical exercise can modulate the expression of lncRNAs, influencing cardiovascular disease progression. Therefore, understanding this relationship could help identify prospective biomarkers and therapeutic targets pertaining to cardiovascular ailments. This review has underscored recent advancements concerning the potential biomarkers of lncRNAs in cardiovascular diseases, while also summarizing existing knowledge regarding dysregulated lncRNAs and their plausible molecular mechanisms. Additionally, we have contributed novel perspectives on the underlying mechanisms of lncRNAs, which hold promise as potential biomarkers and therapeutic targets for cardiovascular conditions. The knowledge imparted in this review may prove valuable in guiding the design of future investigations and furthering the understanding of lncRNAs as diagnostic, prognostic, and therapeutic biomarkers for cardiovascular diseases.

Inflammation is a key contributor to cardiovascular disease (CVD), yet existing risk models such as Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) and Pooled Cohort Equations (PCE) inadequately identify individuals at intermediate risk. We investigated whether incorporating the inflammatory chemokine CCL17 could improve cardiovascular risk prediction. In two prospective cohorts-the Shunyi Cohort (n = 706, China) and the UK Biobank (n = 36,097, UK)-baseline CCL17 levels were quantified, and major adverse cardiovascular events (MACEs) were tracked over follow-up. Elevated CCL17 levels were independently associated with increased risk of MACEs. Integrating CCL17 into existing models significantly improved discrimination and reclassification, particularly among intermediate-risk individuals (e.g., NRI: 15.1% in Shunyi; 3.0% in UK Biobank). This biomarker-based refinement enabled earlier identification of clinically significant high-risk individuals. These findings suggest that CCL17 is a promising translational biomarker that may enhance precision prevention by augmenting current cardiovascular risk assessment strategies.

Cardiac surgery with cardiopulmonary bypass (CPB) may lead to many postoperative complications. However, many complications cannot be predicted in time using the current clinical methods, or the prediction is not sufficiently accurate, resulting in a delay in treatment. Extracellular vesicles (EVs) are a group of membrane vesicles generated from various sources, including endothelial cells and platelets, upon activation or apoptosis. Here, we summarize the role of circulating EVs in predicting complications after cardiac surgery with cardiopulmonary bypass. We found that EV levels can predict acute heart failure. EV subtypes can predict acute heart failure, acute kidney injury, acute lung injury, blood transfusion, and neurological complications. The components of EVs can predict acute heart failure, acute kidney injury, acute lung injury, and neurological complications. The size distribution of EVs can predict acute lung injury. Therefore, circulating EVs can be used to predict complications after cardiac surgery with cardiopulmonary bypass.