Journal of Cardiovascular Translational Research最新文献

Cachexia is a complex syndrome often affecting chronic heart failure (CHF) patients, characterized by muscle wasting and systemic inflammation. Early detection is crucial for improving patient outcomes. This study evaluated candidate inflammatory and nutritional biomarkers, including a novel C-reactive protein-to-albumin ratio (CAR) modification adjusted for body mass index (CARB), in predicting cachexia and muscle depletion in CHF patients. By analyzing 154 newly diagnosed CHF patients, 25 candidate inflammatory-nutritional biomarkers were examined. Muscle depletion parameters (fat-free mass-FFM, fat-free mass index-FFMI, appendicular lean mass-ALM, appendicular skeletal muscle-ASM) were assessed using bioelectrical impedance analysis and the Global Leadership Initiative on Malnutrition (GLIM) criteria. CARB was found to be the most significant predictor of cachexia (OR = 4.89) and muscle mass reduction (OR = 2.450 for FFMI; OR = 3.530 for ASMI). CARB demonstrated excellent diagnostic accuracy (AUC = 0.930) and is a promising candidate biomarker for predicting cachexia and muscle depletion in CHF.

Myocardial repolarization and QT duration are crucial markers for diagnosis and monitoring of congenital long QT syndrome (LQTS). Here we present a novel algorithm to automatically estimate the QT interval based on Lepeschkin's tangent method, as well as parameters underlying T-wave morphology in digital electrocardiograms (ECGs) of 466 patients with LQTS. The algorithm's performance was validated using ECG data from 40 healthy controls. The results were compared against expert measurement of the QT interval, as well as against the results of the ECG device MUSE™ system. Applying an optimizable Support Vector Machine classifier on the algorithm's outcomes achieved an accuracy of 78.1% and area under the curve of 0.85 in classifying LQTS patients with a prolonged QTc interval (upon QT_GS) from those with a normal QTc interval. The presented MATLAB®-based algorithm offers a transparent and reproducible approach to automatic QT interval estimation and QTc calculation in LQTS patients, potentially improving automatized screening, diagnostic precision and patient management.

We aimed to evaluate a novel polymer-free hybrid drug eluting stent (DES) relative to benchmark devices and specific controls addressing singular components of the test device in a juvenile pig model of coronary stenting. 80 stents were implanted in 28 juvenile pigs and evaluated at 28 and 90 days using quantitative coronary angiography and histopathology (n = 10 per group). Scanning electron microscopy was used at 14 days to assess early re-endothelialization (n = 3 per group). The test device featured a cobalt-chromium (CoCr) backbone with a polymer-free probucol matrix releasing everolimus. The polymer-free test stent showed improved strut coverage at 28 days compared to the polymer-coated control, with significantly lower neointimal growth at 90 days and near complete endothelialization at 14 days. This preclinical study supports the favorable vascular healing profile of a polymer-free hybrid DES, warranting further clinical investigation.

Neutrophil extracellular traps (NETs) are implicated in thrombosis and inflammation during acute myocardial infarction (AMI), but their kinetics, local distribution, and clinical relevance remain unclear. We conducted a prospective study in 144 patients with ST-segment elevation (STEMI) and non-ST-segment elevation AMI (NSTEMI) undergoing coronary angioplasty (PCI), quantifying double-stranded DNA (dsDNA), myeloperoxidase (MPO), and neutrophil elastase (NE) in the infarct-related artery (IRA), contralateral coronary artery (CCA), and peripheral blood. Coronary thrombi and DNASE1 Q222R were also analysed. NET markers were elevated in the IRA, and NE and dsDNA increased peripherally after PCI. IRA NE levels independently predicted cardiovascular events (HR, 1.76; 95%CI: 1.24 - 2.51). Thrombi with higher NE and citrullinated histone H3 content were associated with suboptimal PCI results. dsDNA levels were significantly higher in patients with the GG DNASE1 genotype. These findings indicate a compartmentalized NET response in AMI and support a potential prognostic impact of NETs.

Coronary artery disease (CAD) is increasingly recognized as a chronic inflammatory condition. Interleukin-27 (IL-27), a cytokine from the IL-12 and IL-6 families, plays a dual role in CAD pathogenesis. It exacerbates disease by interacting with IL-1β and activating the NLRP3 inflammasome, promoting inflammation and tissue damage. Conversely, IL-27 can delay disease progression by engaging STAT1/3 signalling, suppressing inflammation, and promoting tissue repair. Future research should focus on elucidating IL-27's specific biological functions, interactions with molecular targets, and clinical implications in CAD. This will enhance understanding of CAD and support the development of improved diagnostic and therapeutic strategies.

The aim of this study was to develop and validate a machine learning tool for predicting survival in PAD patients who received surgical treatment. We used the data from 1,615 patients who underwent PAD surgery from 2005 to 2020. Gradient boosted decision trees (GBDTs) were used to predict mortality at one, three and five years after the first surgery, while predictor importance was assessed using the SHAP values method. The area under the curve (AUC) of the receiver operating characteristic curve of the one-, three and five-year prediction models were 0.86, 0.84 and 0.80, respectively. Disease stage was the most important predictor, along with age, chronic kidney disease status, hospital length-of-stay and total number of comorbidities. Presence of dyslipidemia was slightly predictive of one- and three-year mortality. Simple clinical and demographic parameters can be used to train a GBDT model capable of predicting PAD follow-up mortality.

Myocardial ischemia/reperfusion injury (MIRI) worsens ischemic damage, with ferroptosis as a key mediator of this iron-dependent cell death. Lactylation, a novel epigenetic modification, remains poorly understood in MIRI-associated ferroptosis. This study aimed to elucidate the mechanistic link between lactylation and ferroptosis in MIRI. Experimental results demonstrated that hypoxia/reoxygenation (H/R) induction combined with lactate (LA) treatment significantly enhanced the protein expression levels, lactylation status, and protein stability of acyl-CoA synthetase long-chain family member 4 (ACSL4). Site-specific analysis identified lysine 83 (K83) as the critical lactylation modification site on ACSL4. Functional studies revealed that LDHA knockdown-mediated suppression of lactate levels attenuated ferroptosis in H/R-treated cells, an effect that was reversed by ACSL4 overexpression. In vivo validation confirmed that LDHA depletion ameliorated ferroptosis-related damage and mitigated MIRI-induced cardiac dysfunction. Collectively, these findings establish that lactylation-regulated ACSL4 ferroptosis exacerbates MIRI pathogenesis, suggesting that targeting the lactylation-ACSL4 axis represents a promising therapeutic strategy for MIRI.

Chronic social stress is increasingly recognized as a significant contributor to endothelial dysfunction, a key precursor to various cardiovascular diseases. This review endeavors to explain the intricate molecular pathways underlying endothelial dysfunction triggered by chronic social stress and to explore its implications for treatment. We summarize the roles of neurotransmitters, neuromodulators, and immune factors in mediating stress-induced vascular changes. We examine recent advances in pharmacology aimed at targeting these pathways, presenting potential avenues for therapeutic intervention. Understanding these molecular mechanisms not only enhances our comprehension of stress-related vascular disorders but also offers the potential for developing targeted therapies to alleviate their adverse effects on cardiovascular health. This review underlines the importance of unraveling molecular pathways and highlights therapeutic opportunities for managing endothelial dysfunction resulting from chronic social stress.

We tested whether platelet microRNAs (miRs) expression can predict bleeding in patients supported with the HeartMate3 (HM3) left ventricular assist device (LVAD). The levels of expression of platelet miR-126, miR-233, miR-151a, and miR-454 were prospectively measured in 12 consecutive patients pre-implant and during long-term follow-up and compared based on aspirin (ASA) or ASA-free therapy at discharge and bleeding events over the course of HM3 support. Median time of follow-up was 760 (574-844) days. Seven (58%) patients were discharged on ASA and 5 (42%) without ASA. Three (25%) patients experienced 10 bleeding episodes: one never received ASA, and two suffered from bleeding recurrency long after permanent ASA discontinuation. ASA had minimal influence on platelet miRs expression. The expression levels of platelet miR-454 were lower in bleeders vs. non-bleeders, both pre-implant and post-implant. This study suggests the existence of a patient-specific pro-hemorrhagic phenotype associated with a distinctive expression profile of platelet miR-454. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03255928 . ClinicalTrials.gov Identifier: NCT03255928.

Myocardial markers and inflammatory factors have been identified as risk factors for the development of sepsis-induced cardiac dysfunction (SIC), the prognostic significance and clinical utility of utilizing a multi-index combined prognostic approach remain uncertain. Our objective was to establish a "risk score" utilizing clinical indexes to provide short-term prognostic insight for individuals with SIC. Utilizing Lasso regression and COX regression analysis, we identified a history of diabetes, CRP, and NT-proBNP on day 3 as independent risk factors for 28-day mortality in SIC patients. Specifically, the Cox regression analysis identified a hazard ratio of 24.74 (95% CI: 5.90-103.71) for the high-risk group. The prognostic thresholds for CRP and NT-proBNP were determined to be 83.3 mg/L and 1720.7 ng/L, respectively. In conclusion, a "risk score" predictive model incorporating diabetes history, CRP, and NT-proBNP was developed to assess 28-day mortality in patients with SIC.