Journal of Cardiovascular Translational Research最新文献

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.

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.

Pathological growth of cardiomyocytes known as cardiac hypertrophy (CH). Differential expressions of miRNAs have an immense therapeutic potential against cardiac hypertrophy. The current study aim is to evaluate the therapeutic potential of miRNA-137-3p/383-5p in cardiac hypertrophy by regulation of PGC-1α signaling nexus. Silencing of pro-hypertrophic miRNAs e.g. miR-137-3p and miR-383-5p leads to the restoration of their common target gene PGC-1α in hypertrophic cells. Interestingly, the results of this invivo study showed the cardioprotective effects of these antagomirs. Moreover, PGC-1α associated signaling events e.g. fatty acid oxidation (Cpt1a, Cpt1b), mitochondria membrane potential (MMP), mitochondrial reactive oxygen species (mtROS), oxidative phosphorylation (Ndufa6, Atp5me), apoptosis (Bcl-2, BAX), antioxidants (SOD, GSH, CAT), mitochondrial dynamic (Mfn-2, Drp-1) were significantly restored in the treated groups of miRNA antagomirs. Conclusively, this study uncovers that the pharmacological inhibition of miR-137-3p and miR-383-5p have a potential to rescue from the cardiac hypertrophy by regulation of PGC-1α signaling nexus.

Small Interfering RNA (siRNA) is a class of double-stranded, noncoding RNA that silences pathogenic mRNA through the process of RNA interference (RNAi). Its medical application is extensive, particularly in targeting genes associated with cardiorenal diseases, including atherosclerosis, chronic kidney disease, hypertension and cardiac failure. The pathophysiology of cardiorenal syndrome is intricate, involving a network of neurohormonal, metabolic, hemodynamic, and inflammatory interactions. Thereby, this review emphasizes the mechanistic pathways and provides evidence from preclinical and clinical studies underscoring the therapeutic potential of siRNA in the cardiorenal axis. siRNA has been shown to alleviate hemodynamic stress, reduce inflammatory cytokines and disease biomarkers. Additionally, advancements in delivery systems are explored, with a focus on overcoming challenges such as poor stability, off-target effects and limited absorption to enhance clinical applicability. This review highlights the development of siRNA-based therapeutic strategies within the cardiorenal axis, emphasizing a molecular understanding of the underlying mechanisms.

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.