Journal of Cardiovascular Translational Research最新文献

Cardiogenic shock (CS) following myocardial infarction remains highly fatal. The prognostic value of dynamic metabolic markers-particularly glucose and cortisol-remains incompletely understood. In this prospective cohort study, 41 patients with infarction-related CS underwent serial blood sampling over 96 h. Plasma glucose and serum cortisol levels were measured repeatedly. Primary endpoint was in-hospital mortality. Admission glucose levels stratified as < 10, 10-15, and > 15 mmol/L were associated with rising mortality (36.4%, 43.8%, 50.0%; p = 0.47). Mortality was higher in patients without known diabetes. Early glucose normalization (≤ 6 h) correlated with improved survival (25% vs. 45%; p < 0.05). Cortisol levels were markedly elevated on admission. Survivors showed rapid decline; non-survivors had persistently high levels. Cumulative cortisol exposure (AUC₀-₉₆) was significantly lower in survivors (p = 0.016). Serial metabolic profiling identified early and sustained hyperglycaemia and hypercortisolaemia as independent predictors of mortality in infarction-related CS and potential targets for intervention.

Sarcoidosis is a heterogenous, multi-systemic granulomatous disease with highly variable incidence (5-40/100,000) and a disproportionate mortality burden in those presented with pulmonary fibrosis or cardiac involvement. Yet, current management strategies are symptom-targeting, not always effective and come with significant side effects. Preclinical murine models of sarcoidosis have shown that aberrant mTORC1 activation promotes macrophage-driven inflammation and disrupts autophagic clearance, sustaining granuloma formation. Sirolimus, a selective mTORC1 inhibitor, restores autophagy and macrophage function, offering a targeted therapeutic approach. Herein, we present the first comprehensive review of all known clinical cases of sirolimus use in different forms of sarcoidosis. All studies reviewed suggest that sirolimus may be an effective, yet safe, mechanism-targeting therapy for patients with sarcoidosis not responding to conventional pharmacological interventions.

Diabetic cardiomyopathy (DCM), defined as cardiac impairment resulting from the development of diabetes mellitus, has emerged as a global epidemic. DCM primarily denotes myocardial metabolic impairment induced by elevated glucose levels, with hyperglycemia serving as a separate risk factor for heart disease in a lack of hypertension and coronary atherosclerosis. Exosomes, a category of tiny extracellular vesicles essential for communication between cells, have attracted considerable interest for their prospective use in the investigation and management of DCM. Exosomes harbour bioactive chemicals that indicate specific physiological conditions, modulate bioenergetic metabolism, and facilitate tissue healing. This review elucidates the dynamic progression of exosome research in DCM through bioenergetic disruptions, encompassing different processes such as endothelial dysfunction, mitochondrial impairment, calcium signalling in the endoplasmic reticulum, cell death including apoptosis and ferroptosis, inflammation-related fibrosis, autophagy, and hypertrophy. It emphasizes the necessity for continued research to fully exploit the potential of exosomes in enhancing patient outcomes.

Exosomes are small vesicles secreted by a variety of cells surrounded by a lipid bilayer membrane and containing a variety of biomolecules, of which microRNAs (miRNAs) are the most abundant. Exosomal miRNAs are involved in the development of cardiovascular diseases(CVD), and their unique biological properties make them expected to be effective targets for the treatment of CVD. This article reviews the biological characteristics, expression, and mechanism of action of exosomes and exosomal miRNAs in CVD, as well as their potential as biomarkers in the diagnosis, treatment, and prognostic assessment of CVD, to provide new ideas in the field of CVD medicine.

Recent studies emphasize the beneficial effects of exercise on diabetic cardiomyopathy (DCM), adding to the growing body of evidence that underscores the role of exercise in improving health outcomes. Despite this, a notable gap persists in the number of healthcare providers who actively prescribe exercise as a therapeutic intervention for DCM management. In addition, exercise modulates the expression of lncRNAs, which play a pivotal role in DCM progression. Further investigation into this relationship may facilitate the identification of novel biomarkers and therapeutic targets for DCM. This review consolidates recent advances in identifying lncRNAs biomarkers in DCM, summarizing the current knowledge on dysregulated lncRNAs and their molecular mechanisms. Additionally, it offers new insights into the mechanistic roles of lncRNAs, highlighting their potential as biomarkers and therapeutic targets for DCM. Overall, this review aims to inform future research and reinforce the significance of addressing diabetes-related cardiovascular diseases to potentially improve clinical outcomes.

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.