Journal of Cardiovascular Translational Research最新文献

To develop a predictive model for optimal anastomosis sizing in TAPVC surgery, focusing on the role of pulmonary venous confluence (PVC) size. A patient-specific fluid-structure interaction (FSI) model simulated blood flow through various anastomosis sizes. Key variables included body weight, anastomosis length, and PVC size. The model's predictions were validated against postoperative echocardiographic measurements from nine TAPVC cases. A strong positive correlation was found between flow velocity and the ratio of body weight to anastomosis length and PVC circumference. Including PVC size significantly improved predictive accuracy. No significant difference was observed between predicted and measured velocities. PVC size is a critical factor for planning TAPVC surgery. Incorporating it into computational models enhances the prediction of flow dynamics and supports personalized surgical decision-making.

Tricuspid regurgitation (TR) is a highly morbid and often untreated valvular heart disease. New devices are under development to address this unmet need, necessitating valid models to test their efficacy. Aim of this study was to assess feasibility and reliability of pulmonary artery banding (PAB) as a pathological acute model of functional TR. Eight pigs underwent right thoracotomy, with an umbilical tape placed around the main pulmonary trunk, followed by controlled reduction of the pulmonary artery lumen via a tourniquet system. No animals died during the procedure. After PAB, right ventricular (RV) mean pressure, RV basal and mid-diameter and tricuspid septo-lateral diameter significantly increased (+ 97%, + 23%, + 32%, + 20%, p < 0.01 for all). Consequently, TR was at least moderate-to-severe in all the animals and these modifications remained stable for up to one hour. PAB therefore represents a reliable, one-step model of functional TR ideal to test the efficacy of new tricuspid devices.

Chronic myocardial ischemia (CMI) is a key pathological condition in coronary artery disease (CAD), yet small animal models for CMI are limited. This study developed and characterized a CMI mouse model using ApoE-/- mice fed a high-fat diet for 3 months. Cardiac function was assessed through electrocardiography (ECG), myocardial action potential, and perfusion echocardiography. The model group exhibited elevated cholesterol, aortic lipid plaques, and T-wave flattening, correlated with atherosclerosis severity. Impaired myocardial perfusion, reduced ATP content, and accelerated inner cardiomyocyte repolarization were also observed. PET/CT scans revealed filling defects, while myocardial contractile function showed reactive suppression under CMI conditions. This model replicates CMI's pathological features, providing a valuable tool for studying CAD progression and treatment.

Hyperoside (Hyp) exhibits notable protective effects by targeting oxidative stress, ferroptosis, and apoptosis. In vivo experiments used a murine model of DOX-induced cardiotoxicity with Hyp co-treatment. Hyp co-administration mitigated doxorubicin-induced cardiac impairment in mice, demonstrated by enhanced ejection fraction (EF) and fractional shortening (FS), diminished inflammatory cell infiltration and fibrotic changes, reduced circulating levels of cardiac biomarkers including cTnT, CK, CK-MB, LDH, and LDH-1. Hyp reduced oxidative stress (lower MDA, higher SOD and GSH-Px activity), inhibited ferroptosis (decreased intracellular Fe2 + , MDA, 4-HNE, PTGS2, and ASCL4; increased GSH and Ferritin), and suppressed apoptosis (fewer TUNEL-positive cells, balanced Bax/Bcl-2). Mechanistically, Hyp activated the Nrf2/GPX4 axis: it promoted Nrf2 nuclear translocation, upregulated GPX4 expression as shown by molecular docking. These effects were abrogated by ML385, confirming Nrf2 dependence. Hyp alleviates DOX-induced cardiotoxicity via Nrf2/GPX4 activation, suppressing oxidative stress, ferroptosis, with potential as a therapeutic agent.

This study evaluated coronary computed tomography angiography (CCTA)-based computational fluid dynamics (CFD) for predicting plaque dynamics in coronary artery disease. We retrospectively analyzed 22 patients (34 lesions) with paired CCTAs (mean interval 2 years). Lesions were categorized as progression (increase in diameter stenosis ≥ 5%), stable (change within - 5% to 5%), or regression (decrease in diameter stenosis ≥ 5%). Hemodynamic indices were normalized to adjacent non-diseased segments. Logistic regression identified predictors: normalized minimum wall shear stress (odds ratio (OR) = 0.38, p < 0.001) and maximum helicity (OR = 1.44, p = 0.016) predicted progression; average vorticity (OR = 0.13, p = 0.019) and gradient oscillatory number (OR = 0.10, p = 0.001) predicted regression. Receiver operating characteristic (ROC) analysis showed good discrimination (area under the curve (AUC) = 0.78 for progression, 0.83 for regression). These noninvasive imaging- and hemodynamic-derived markers, which were independently associated with lesion progression, may enhance coronary artery disease risk stratification by identifying high-risk plaques beyond stenosis severity, thereby informing individualized follow-up and treatment.

Coronary artery calcification (CAC), a key atherosclerotic pathology, has shifted from a passive degenerative marker to an actively regulated process involving osteogenic transdifferentiation, inflammation, and cellular diversity. This review summarizes 30 years of research, integrating pathological mechanisms, technological advances, and clinical evidence for CAC management. Single-cell sequencing identifies distinct intimal (atherosclerosis-linked) and medial (CKD/diabetes-related) subtypes driven by pathways like BMP2/Smad and OPG/RANKL. Innovations include intravascular lithotripsy (IVL, ≥ 98% success in severe calcification) and AI improving imaging accuracy (99.2% segmentation). Challenges remain: statins' dual effects on calcification, subtype diagnostic gaps, and limited access to advanced tools (IVL unavailable in > 70% of resource-limited facilities). The synthesis highlights needs for multi-omics precision therapy, AI-based risk stratification, and cost-effective solutions to shift from reactive treatment to proactive vascular health optimization, addressing the rising burden of calcific cardiovascular disease in aging populations.

Extracellular vesicles (EVs) have been implicated in cardiac remodeling during heart failure (HF). However, the role of circulating EVs (CEVs) in the process of HF is poorly understood. To elucidate the molecular mechanism associated with CEVs in the context of HF, the proteome of 4D label-free EVs from plasma samples was identified. Among the identified proteins, 6 exhibited upregulation while 9 demonstrated downregulation in CEVs derived from HF patients (HCEVs) compared to healthy controls (NCEVs). Our results showed that up-regulated proteins mainly participate in the primary metabolic, glycerolipid metabolic processes, oxidation-reduction process, and inflammatory amplification. In contrast, the down-regulated proteins influenced cell development, differentiation, and proliferation. Compared to NCEVs, HCEVs significantly induced inflammation and triacylglycerol (TAG) accumulation in human cardiomyocytes (HCMs) in vitro. They also compromised their regenerative capacities, triggered endoplasmic reticulum (ER) stress and increased autophagy in HCMs. Further, HCEVs induced differentiation of human cardiac fibroblasts (HCFs), amplifying pro-inflammatory, and pro-fibrotic factors, and enhancing extracellular matrix deposition. Notably, HCEVs are also associated with an increase in the HF biomarker MMP9 within HCFs and demonstrate a negative correlation with autophagic flux. In conclusion, HCEVs appear pivotal in advancing HF via pathological cardiac remodeling.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet current therapies-including drugs and catheter ablation-remain suboptimal. Gene therapy offers a promising way to modulate AF's molecular drivers. This review summarizes recent preclinical studies using viral and non-viral vectors, atrial-specific delivery strategies, and key targets such as ion channels, fibrosis, and oxidative stress. Despite promising results, no AF gene therapy has FDA approval, due to challenges in atrial targeting, immune control, and durable expression. Closing this translational gap is critical for future AF gene therapy.

RNA-based therapeutics, such as small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs) and messenger RNAs (mRNAs) are promising therapeutics that offer new avenues for targeting molecular pathways underlying heart failure (HF) pathogenesis. This review provides an overview of RNA therapeutics, detailing their mechanisms and potential applications in the treatment of HF. Key pathological processes in HF, including dysregulated calcium handling, myocardial fibrosis, oxidative stress, inflammation and aberrant signalling, are explored to identify how RNA-based therapeutics can be utilized to address these mechanisms. Preclinical studies demonstrating the potential of RNA therapeutics to modulate these pathways are discussed. In addition, the review identifies novel therapeutic targets of HF that may allow more precise and effective interventions, potentially reversing disease progression in HF. In this way, the potential of RNA therapeutics as a next-generation treatment strategy for HF are highlighted, offering hope for more targeted and personalized approaches for HF.

Myocardial ischemia-reperfusion injury (IRI) is a major issue in cardiovascular medicine, marked by tissue damage from the restoration of blood flow after ischemia. Opioids, known for their pain-relieving properties, have emerged as potential cardioprotective agents in IRI. Recent research suggests opioids influence epigenetic mechanisms-such as histone modifications and non-coding RNAs (ncRNAs)-which are essential for regulating gene expression and cellular responses during myocardial IRI. This review delves into how opioids like remifentanil affect histone modifications, DNA methylation, and ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Remifentanil postconditioning (RPC) reduces apoptosis in cardiomyocytes through histone deacetylation, specifically downregulating histone deacetylase 3 (HDAC3). Similarly, opioids impact miRNAs such as miR- 206 - 3p and miR- 320 - 3p, and lncRNAs like TINCR and UCA1, which influence apoptosis, inflammation, and oxidative stress. Understanding these interactions highlights the potential for opioid-based therapies in mitigating IRI-induced myocardial damage.