Journal of Cardiovascular Translational Research最新文献

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.

Diagnostic potential of sialin in identifying endothelial dysfunction is explored. 50 CAD patients, 50 young (20-35 years) dyslipidemic individuals (DLP), and 50 healthy controls (HC) were included in the study. HUVECs were stimulated with either TNFα or AT-2. RNA isolation, Real-time PCR, ELISA, and immunofluorescence staining were performed. In silico analysis was performed. ROC curves were constructed. Stimulated ECs showed increased sialin mRNA expression. Sialin mRNA peaked in the supernatant at 1-6 h, decreasing by 24 h. Serum sialin mRNA was significantly higher in DLP patients than in HC and CAD patients, whereas CXCL14 mRNA was elevated in CAD patients. Sialin mRNA had high sensitivity/specificity for predicting endothelial dysfunction. In silico analysis revealed the binding of translational repressor RNPs to the 5'UTR of sialin mRNA. This is the first study highlighting circulating sialin mRNA as a novel biomarker for endothelial activation.

The acute pathophysiological changes after myocardial ischemia complicated by cardiogenic shock (CS) remain poorly defined, especially regarding compensatory mechanisms and myocardial mitochondrial function. We investigated immediate cardiovascular and mitochondrial effects in a porcine model of ischemic CS. CS was induced in 32 Danish Landrace pigs (60 kg) via repeated microembolization of the left coronary artery until a 30% reduction in cardiac output (CO) or mixed venous saturation. Monitoring included pulmonary artery and left ventricular pressure-volume catheters, with analysis of endomyocardial biopsies and arterial, mixed venous, and coronary sinus blood samples. CO deteriorated promptly due to decreased stroke volume. Contractility declined, and afterload increased, causing rapid ventriculo-arterial decoupling. Forward flow parameters were compromised prior to pressure-parameters. Diastolic function was impaired and mitochondrial damage was observed. CS rapidly impairs LV hemodynamic and mitochondrial function, highlighting the importance of monitoring forward flow and targeting mitochondrial function in treatment.

The heart grows in response to both pathological and physiological stimuli. Pathological hypertrophy often leads to cardiomyocyte loss and heart failure (HF), whereas physiological hypertrophy paradoxically protects the heart. Comparing these two types of hypertrophy can elucidate the differences and connections in their molecular mechanisms, which is pivotal for unraveling the pathogenesis of HF. This study compares pathological (TAC-induced) and physiological (exercise-induced) cardiac hypertrophy using single-cell and bulk transcriptomics. Mitochondrial fusion/fission imbalance emerged as a key dysregulated pathway in both models. An early increase in the fusion/fission ratio (2 weeks post-TAC) resembled exercise-induced remodeling, while a progressive decline at 5-8 weeks marked transition to pathological hypertrophy. By 11 weeks, suppressed fusion and increased fission led to heart failure. Downregulation of fusion genes (Mfn1, Mfn2, Opa1) and upregulation of fission genes (Fis1, Dnm1l) highlight mitochondrial dynamics as critical drivers of disease progression.