Journal of Cardiovascular Translational Research最新文献

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.

We compared the effects of ex-vivo machine perfusion (EVMP) of hearts donated after circulatory death (DCD) with the single-shot solutions HTK-N and Del Nido cardioplegia (DNC) on left-ventricular (LV) contractility and myocardial microcirculation. In a DCD pig model, hearts were maintained by EVMP with hypothermic, oxygenated HTK-N (DCD-HTK-N; N = 8) or DNC (DCD-DNC; N = 8) followed by reperfusion with blood, including assessment of contractility and microcirculation with Laser-Doppler-Flow (LDF). We performed transcriptomics using microarrays. In DCD-HTK-N, the ESP, dp/dt_max and dp/dt_min were significantly higher (p < 0.05) compared to DCD-DNC. Relative LDF was higher in DCD-HTK-N vs. DCD-DNC. Pathways related to inflammatory mediators, cAMP, ion channels, intracellular signaling, and cell death were regulated differently. In DCD-HTK-N, longevity-associated pathways were up-, and ageing-associated pathways were downregulated. EVMP of DCD hearts with HTK-N results in a superior LV function, microcirculation, and regulation of pathways with short- and long-term relevance compared to DNC.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides cardiopulmonary support during the critical care. Despite its exponential use over last few decades, clinical studies suggest that it does not improve infarct size and mortality in patients suffering from cardiogenic shock after the acute myocardial infarction (AMI). The effect of hyperoxygenated blood under high pressure on the poor outcomes associated with VA-ECMO have not been tested. In this study we tested the hypothesis whether normoxemic oxygenation of blood during provides protection against VA-ECMO associated cardiac damage using a swine model of AMI. Our results indicate that normoxemic VA-ECMO (PaO2 < 200 mmHg), reduces infarct size, activates pro-survival RISK pathway and furthermore preserves mitochondrial structure and function as compared to hyperoxygenated VA-ECMO (PaO2 > 200 mmHg) in ischemia-reperfusion injury. In absence of conclusive clinical trials testing the effect of VA-ECMO blood oxygenation on the patients' outcomes, our findings provide new mechanistic insight into the myocardial effects of VA-ECMO.

Temporal velocity-informatics (TVI) is a novel technique utilizing spatial analysis of time-resolved 3D velocity fields to quantify flow disturbance in vascular aneurysms. Although it can improve the characterization of intracranial aneurysms' (IA) rupture status, calculation of time-resolved 3D velocity fields using computational fluid dynamics (CFD) simulations limits its clinical translation. This study aims to test the feasibility of using IA's geometrical information in conjunction with machine learning (ML)-based regression methods to predict TVI parameters. The effectiveness of these ML-predicted TVI parameters in predicting IA's rupture status was evaluated using one hundred twelve IAs with known rupture status. We found that predicting the IA's rupture status using predicted TVI can achieve an AUC of 0.88, and a total accuracy of 81.6%. Also, We found that the consistency between ML-predicted TVI variables and estimated TVI metrics calculated from CFD-simulated velocity data was higher than our ability to predict wall shear stress-based metrics.

Platelet reactivity (PR) in clopidogrel-treated patients undergoing percutaneous coronary syndrome (PCI) associates with ischemic and bleeding risk. The aim was to investigate the association of PR and global hemostasis with this risk in patients with atrial fibrillation (AF) undergoing PCI. TEG was performed on day 1-3 after PCI. 168 patients were included. Mean age was 79 years (IQR 72-82). 101 (60%) patients had high platelet reactivity (HPR). HPR was not associated with the composite outcome of MACE (HR 1.23 [ CI 95% 0.43-3.49], p = 0.700). 33(19.6%) patients had HPR and increased platelet-fibrin clot strength and showed a trend for association with higher ischemic risk (HR 2.83 [CI 95% 0.70-8.06], p = 0.078). Rates of HPR in patients with AF undergoing PCI were high. Neither HPR nor LPR predicted ischemic or bleeding risks. Patients with HPR and increased platelet-fibrin clot strength may be at higher risk for ischemic events.

Atherosclerosis (AS) is a vascular disorder characterized by lipid accumulation, fibrous tissue proliferation, and calcium deposition in the intima, contributing significantly to the mortality associated with cardiovascular disease, and the pathogenesis of AS is multifaceted. Recent studies have identified copper (Cu) overlap induced cuproptosis as a key mechanism underlying cellular dysfunction in AS. Cuproptosis impacts the function and survival of multiple cell types within AS lesions by several downstream pathways, and regulating cellular cuproptosis may be a very promising clinical treatment strategy. In this review, we explored the influence of key regulatory proteins and signaling pathways associated with copper homeostasis and cuproptosis in AS, and the potential regulators of cuproptosis in AS therapy, especially the endogenous metabolites, copper ionophore, Cu oxide nanoparticles and natural products, we also discuss emerging therapeutic strategies and offering insights into future developments and translational medicine or challenge by targeting cuproptosis in AS pathogenesis.