Journal of Cardiovascular Translational Research最新文献

This study aimed to investigate the underlying mechanisms of Fibroblast Growth Factor 21 (FGF21) in myocardial ischemia/reperfusion (I/R) injury. First, FGF21 was upregulated in the serum of patients with myocardial I/R injury as well as in I/R hearts of mice and hypoxia/reoxygenation (H/R) neonatal rat cardiomyocytes (NRCMs). While FGF21 knockout exacerbated such injury, which was mitigated by rhFGF21. Bioinformatics analysis identified immunity-related GTPase M1 (Irgm1) as a key autophagy-related gene downregulated in ventricular tissue of FGF21^-/- I/R mice. Impaired autophagic flux in FGF21^-/- mice during I/R could be rescued by rhFGF21 through the signal transducers and activators of transcription 1 (STAT1) pathway. The beneficial effects of rhFGF21 in reducing H/R injury were limited in Irgm1 knockdown NRCMs. This study suggested that FGF21 deficiency intensifies myocardial I/R injury by exacerbating the impairment of autophagic flux. Activation of FGF21 or Irgm1 may serve as a promising therapeutic strategy for myocardial I/R injury.

Early diagnosis and treatment of atrial cardiomyopathy(ACM) are crucial for patients with atrial fibrillation(AF), and further exploration of its biomarkers remains necessary. High-throughput sequencing of exosomal miRNAs was performed on blood samples from patients with persistent AF (PeAF) exhibiting mild and severe left atrial fibrosis, with supraventricular tachycardia (SVT) patients. Quantitative real-time reverse transcription polymerase chain reaction analysis validated differentially expressed miRNAs (DE miRNAs) from severe left atrial fibrosis PeAF, SVT and health controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted on target genes. Four exosomal DE miRNAs were identified, including miR-5106, let-7e-5p, miR-320c, and miR-382-3p. Exosomal miR-320c was down-regulated in severe left atrial fibrosis PeAF patients, while the other three miRNAs showed no significant changes. Exosomal miR-320c emerges as a potential biomarker for severe left atrial fibrosis and ACM, suggesting its suitability as a therapeutic target.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of fibrous fatty lesions or plaques within the arterial wall, which causes a large amount of morbidity and mortality worldwide. Copper is a mineral nutrient essential for the human body and is essential for maintaining the normal function of multiple human systems, including the cardiovascular system. Imbalance of copper homeostasis has been increasingly considered as a key factor affecting the pathogenesis and disease progression of AS. This article summarizes the complex association between copper ions and AS, focusing in particular on the key roles of copper metabolism, copper homeostasis and copper death. It aims to reveal the mechanism of action of copper ions in AS and explore treatment strategies targeting copper metabolism, copper death and copper homeostasis imbalance in relation to atherosclerosis, with a view to providing new perspectives and strategies for the treatment and prevention of AS.

Cardiovascular diseases (CVDs) remain the global leading cause of mortality, necessitating novel diagnostics and therapies. Extracellular vesicles (EVs)-including exosomes, microvesicles, and apoptotic bodies-serve as key intercellular communicators in cardiovascular system. As carriers of bioactive miRNAs/proteins, EVs regulate inflammation, fibrogenesis, angiogenesis, and cardiac/systemic communication. Their non-invasive accessibility and disease-specific molecular signatures enable diagnostic applications. Endogenous origin and targeting capacity make EV ideal drug delivery platforms, while engineering of surface/content properties enhances their therapeutic specificity. However, key challenges persist in reproducibility, long-term safety profiles, clearance mechanisms, and therapeutic applications. Therefore, we highlight the potential of EVs as engineered drug carriers and their therapeutic promise for CVDs such as myocardial infarction, atherosclerosis, and heart failure. Future clinical translation of EV-based tools offers transformative potential-from cardiovascular diagnostics to regenerative therapies-where collaborative efforts will accelerate the pipeline development of these emerging solutions for clinical CVDs management.

Cardiovascular disease (CVD) is a prominent contributor to global mortality rates, and its prevalence is consistently on the rise. The utilization of deep sequencing-based transcriptome profiling methodologies has yielded empirical support for the notion that the transcriptional activity of the human genome is more expansive than previously postulated. Long Non-Coding RNAs (lncRNAs) are a heterogeneous collection of noncoding transcripts with a length exceeding 200 nucleotides. Transposable elements represent a significant proportion of the human genome, and their potential contribution could be as high as 90%. LncRNAs can exert control over several biological processes through their ability to modulate the transcriptional activity of coding genes, engage in direct protein interactions, and potentially encode proteins. lncRNAs have been acknowledged as significant factors in the causation and progression of myocardial infarction, heart failure, cardiac hypertrophy, arrhythmias, and other pathological processes that have a considerable influence on the prognosis and survival of individuals afflicted with CVD. Moreover, the observable patterns of expression demonstrated by lncRNAs in different CVD scenarios greatly augment their potential as biomarkers and targets for intervention. To lay a strong foundation for future research on the mitigation and management of CVDs, we comprehensively examine current scholarly literature on lncRNAs in the context of cardiovascular disorders. The discourse also involves the potential usefulness of lncRNAs as biomarkers and targets for therapeutic interventions.

Cachexia, often seen in chronic heart failure (CHF), worsens patient outcomes and survival. Early detection is crucial, and circulating miRNAs offer potential as biomarkers linking heart function, inflammation, and cachexia. This study aimed to identify plasma miRNAs associated with cachexia in CHF and assess their diagnostic and prognostic value. Plasma samples from 150 newly diagnosed CHF patients were analyzed using next-generation sequencing (NGS) and validated by qRT-PCR. A signature of elevated miRNA-628 and reduced miRNA-6803 (↑miRNA-628+↓miRNA-6803) was associated with poor nutritional status, abnormal lab results, and higher cachexia risk. Combining this signature with inflammatory markers perfectly distinguished cachectic from non-cachectic patients (AUC=1.0). This profile increased cachexia risk 19-fold and was linked to significantly shorter survival (median 14 vs. 41 months). Thus, the identified miRNA signature offers strong predictive and diagnostic potential and could complement clinical assessments of CHF patients' nutritional status.

As one of the leading causes of death globally, early diagnosis and prevention of cardiovascular disease have become the focus of clinical and public health. Extracellular vesicles (EVs) are small, double-layered membrane structures actively secreted by cells and are widely present in body fluids such as blood, urine, and saliva. They carry various bioactive molecules, including proteins and nucleic acids, and are known for their remarkable stability and easy accessibility, making them promising candidates for identifying cardiovascular disease. This review summarizes the applications of EVs in the early diagnosis of cardiovascular disease, explores the potential biomarkers of proteins and RNAs (such as miRNA, lncRNA, and circRNA) contained within EVs, and discusses the prospects and challenges of EV biomarkers in clinical applications.

Cardiac fibrosis remains a major clinical challenge with limited therapeutic options, and the role of PFKFB3 in its pathogenesis remains unclear. Single-cell RNA sequencing analysis was applied and the results demonstrated that glycolysis was most prominently enhanced in activated cardiac myofibroblasts (myoCFs) in cardiomyopathy. Western blot analysis revealed that PFKFB3 expression was significantly increased in fibrotic hearts and TGF-β1-stimulated myoCFs. Genetic (Pfkfb3^+/-) and pharmacological (3PO) inhibition of PFKFB3 attenuated myoCF activation, proliferation, and migration, while also reducing cardiac fibrosis in isoproterenol- and coronary ligation- induced mouse models. Mechanistically, TGF-β1 upregulated PFKFB3 in a HIF-1α-dependent manner, and extracellular PFKFB3 further promoted fibroblast activation and inflammatory responses. Clinically, elevated plasma PFKFB3 levels, as measured by ELISA, were significantly associated with fibrosis severity in patients with cardiomyopathy. These findings reveal for the first time that PFKFB3 drives cardiac fibrosis dually through intracellular glycolytic regulation and extracellular signaling, highlighting its translational potential.