Journal of Cardiovascular Translational Research最新文献

Myocardial infarction (MI), is a leading cause of global mortality, marked by cardiomyocyte death. This takes place as a result of ischemic injury, the detrimental impacts of oxidative stress, and inflammatory responses. Conventiona pharmacological interventions, are unfortunately limited by a relatively low targeting efficiency and the inability to reverse the fate of cardiomyocyte death. Recent advances in nanotechnology have led to the development of multifunctional nanoparticles, offering innovative solutions to effectively address these complex challenges. These nanoscale platforms have the remarkable capability to enable targeted drug delivery, precisely regulate the microenvironment, and facilitate real-time monitoring of the cardiac repair processes. This development represents a substantial paradigm shift in the treatment of MI. This review integrates the crucial findings obtained from the recent studies focusing on nanoparticle-based strategies for multifunctional cardiac repair after MI, aiming to explore the potential of nanoparticles in the treatment of MI.

Cardiometabolic diseases (CMD) encompass a cluster of cardiovascular disorders primarily driven by metabolic dysregulation, such as obesity-associated cardiomyopathy, hypertensive heart disease, and diabetic cardiomyopathy. The pathogenesis of CMD is closely linked to chronic inflammation, myocardial hypertrophy, and mitochondrial energy metabolism dysfunction. Recently, the succinate-GPR91 pathway, a critical hub for metabolic regulation, has gained attention for its role in CMD. In addition to its function as an intermediate in the TCA cycle, succinate also exerts a range of pathophysiological effects by acting as a signaling molecule through the activation of its receptor, GPR91.Studies indicate that in metabolic disorders such as obesity, hypertension, diabetes,and atherosclerosis, abnormal activation of the succinate-GPR91 axis exacerbates inflammation, accelerates myocardial hypertrophy, and induces mitochondrial dysfunction, contributing to cardiovascular damage. Targeting the succinate-GPR91 pathway may offer novel CMD therapies. This article reviews succinate's role in inflammation, hypertrophy, mitochondrial dysfunction, and other diseases, offering insights for CMD research and treatment.

This study aimed to explore the association between serum ferritin and glutathione peroxidase 4 (Gpx4), markers of ferroptosis, with the severity of coronary artery stenosis and the occurrence of in-stent restenosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients. The study encompassed 396 eligible CAD patients who underwent PCI, followed up for one year. A control group of 100 individuals was selected, matching the baseline data of CAD patients. Compared to healthy controls (HC), CAD patients showed a significant decrease in serum Gpx4 levels and an increase in ferritin levels. Significant disparities were observed in low-density lipoprotein cholesterol, Gensini score, serum Gpx4, and ferritin between the restenosis and no-restenosis groups (p < 0.001). Serum levels of ferritin and Gpx4, markers associated with ferroptosis, correlate with the severity of coronary artery stenosis in CAD patients and the occurrence of in-stent restenosis after PCI.

Acute myocardial infarction (AMI) remains a leading cause of mortality worldwide, highlighting the need for improved diagnostic approaches. While cardiac troponins are the current gold standard, their reliability in early detection and in patients with comorbidities is limited. This review evaluates conventional AMI biomarkers and highlights emerging candidates including non-coding RNAs, cell-free DNA, exosomes, proteins, and metabolites. It also explores the potential of non-invasive samples such as saliva and urine for early detection. After reviewing recent advances in biomarker discovery and detection technologies, this article presents a comprehensive overview of evolving AMI diagnostics. Identifying sensitive and specific biomarker detectable in non-invasive samples has important clinical relevance for improving early diagnosis and guiding prompt treatment. Future efforts should focus on multi-marker strategies, patient-specific diagnostic thresholds, and the clinical validation of novel non-invasive biomarkers.

This study evaluated the effects of irreversible electroporation (IRE), a non-thermal ablation method, on carotid atherosclerotic plaques induced by high-fat feeding combined with balloon dilation in 30 rabbits. Carotid plaques were subjected to IRE ablation (1000 V/cm alone, 2000 V/cm alone, or 1000 V/cm with rapamycin). There were no acute vascular changes post-ablation; however, IRE induced apoptosis and polarity of cells. At 7-30 days post-ablation, there was a significant decrease in lipid density within the plaque, with replacement by multilayered anterograde smooth muscle cells. Remodeling led to residual plaque becoming sandwiched between the new and original smooth muscle layers and to vessel wall thickening but with improved elasticity. Addition of rapamycin delayed remodeling. IRE reduced lipid deposition, triggered structural vascular reorganization, and improved elasticity, suggesting a potential therapeutic role in atherosclerosis. The tissue selectivity of this technique and non-thermal mechanism may offer advantages over conventional treatments.

The objective of this study was to identify plasma lipid signatures associated with plaque vulnerability. We retrospectively evaluated coronary plaque in 99 patients using optical coherence tomography (OCT) and quantified 489 plasma lipids. We identified intra- and inter-class crosstalk among ceramide (Cer)-phosphatidylinositol (PI)-esterified cholesterol (CE)-sphingomyelin (SM) (Cer-PI-CE-SM) in patients with thin-cap fibroatheroma (TCFA). CE-16:0, SM d18:1/16:1, and GM3 d18:1/22:0, emerged as potential markers of TCFA, correlating with the thinnest fibrous cap thickness and the presence of cholesterol crystallization. Compared to the clinical model (area under the curve [AUC] = 0.810), the AUC of the combined clinical-lipid model improved [AUC = 0.880, p = 0.032]. Calibration and decision curves demonstrated that the combined model exhibited superior diagnostic performance. We identified lipid molecules that are strongly correlated with plaque vulnerability, thus providing an option for the non-invasive identification of vulnerable plaques, which could potentially facilitate the tailored treatment for high-risk patients.

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent hereditary cardiovascular diseases. Eicosanoids are known to play a significant role in cardiovascular diseases and serve as biomarkers. In this study, plasma eicosanoids were profiled by LC-MS in a cohort of 78 healthy individuals and 73 patients diagnosed with HCM. Our findings reveal HCM patients exhibit downregulation of various eicosanoids, including AA, 5,6-DHET, 12-HETE, LXA4, EPA, etc. Notably, the combined predictive model incorporating 12-HETE and EPA demonstrates significant diagnostic value for HCM. Additionally, ten closely related metabolites showed significant positive correlations within the metabolic network graph. Eicosanoids such as 17,18-EEQ, LXA4, and 13-oxo-ODE exhibit significant negative correlations with plasma concentrations of hs-CRP and NT-proBNP in patients. Alterations in eicosanoid metabolism may be implicated in the pathophysiological processes underlying HCM.

Heart failure with mildly-reduced ejection fraction (HFmrEF) lacks therapeutic strategies due to heterogeneity and dynamic transitions between HFrEF/HFpEF. Proteins constitute predominant drug targets and primary mediators of signaling pathways in HF. We measured 92 plasma proteins (Olink CardiovascularIII) in 230 HF patients from BIOMS-HF registry. Fifteen, eighteen, and fifteen baseline proteins discriminated MACEs were determined in HFmrEF, HFpEF, and HFrEF, respectively. Pathway enrichment revealed shared signaling in HFmrEF/HFpEF (apoptosis, etc.), HFmrEF/HFrEF (vascular regulation, etc.), and HFmrEF/HFrEF/HFpEF (inflammatory/hormonal signaling). Four patient phenotypes were identified according to proteomic signatures using unsupervised learning: Cluster1 (younger, smokers, lowest MACEs [29.5%]); Cluster2 (elderly, higher comorbidity, diastolic dysfunction); Cluster3 (systolic dysfunction, elevated heart rates, responsive to HFrEF therapies); Cluster4 (high inflammation, cardiometabolic disturbances, highest MACEs [74.4%]). Cross-referenced with druggable genome database, TNF-R1 was revealed as an appealing druggable target for cluster2/4, while OPN and MMP-2 for cluster3/4. Unsupervised learning based on proteomics identified four HFmrEF phenotypes, each providing druggable targets according to distinct pathophysiological pathways.

Assessment of volume status is essential in heart failure (HF) management, yet the relationship between cardiac filling pressures and true intravascular volume remains unclear, especially in patients with obesity. We analyzed 262 ambulatory HF patients who underwent blood volume analysis (BVA) and same-day right heart catheterization. Patients were stratified by BMI into non-obese (n = 104), obese (n = 121), and morbidly obese (n = 37). Cardiac filling pressures showed modest correlations with directly measured total blood volume (TBV); RAP correlated with TBV %deviation (r = 0.36-0.58), while PCWP correlations were weaker (r = 0.19-0.36) and non-significant in morbidly obese patients. Concordance between pressure and volume was highest in non-obese patients (RAP/TBV 79.8%, PCWP/TBV 69.2%) and lower in obese (66.1%, 55.4%) and morbidly obese individuals (64.9%, 67.6%). Approximately one-third or more of obese patients exhibited discordant pressure-volume profiles. These findings suggest that in obesity, cardiac filling pressures may not reliably reflect volume status.

Ferroptosis plays a key role in abdominal aortic aneurysm (AAA) development. This study explores whether and how ferroptosis regulates AAA progression. Ferroptosis was confirmed in human AAA tissue. In vitro experiments with primary mouse vascular smooth muscle cells (VSMCs) and abdominal aortic rings revealed that angiotensin II (Ang II) triggered ferroptosis in VSMCs. Ferrostatin-1 (Fer-1), a potent ferroptosis inhibitor, effectively suppressed this effect. Additionally, the ferroptosis inducer erastin and Ang II can both promoted pathological remodeling of abdominal aortic rings, but Fer-1 significantly suppressed these effects. In AAA mouse model, Fer-1 treatment reduced AAA formation. Mechanistically, RNA-sequencing analysis revealed that Fer-1 regulates VSMC contractile function, suppresses inflammation, and mitigates extracellular matrix remodeling. These findings highlight the critical role of VSMC ferroptosis in AAA pathogenesis and demonstrate that ferroptosis inhibition effectively reduces pathological vascular remodeling, making it a promising therapeutic strategy for preventing AAA.