Journal of Cardiovascular Translational Research最新文献

Cardiac fibrosis, marked by excessive extracellular matrix accumulation, is a key endpoint in various cardiac diseases and is linked to energy metabolic disorders. This review explores the relationship between mitochondrial energy metabolism and cardiac fibrosis, focusing on the metabolic reprogramming in fibroblasts and cardiomyocytes during fibrosis development. We examine changes in substrate utilization, oxidative phosphorylation (OXPHOS), and ATP production that characterize the fibrotic heart. The metabolic dysregulation involves disruptions in fatty acid oxidation, glucose metabolism, and amino acid metabolism, contributing to fibrosis pathogenesis. Additionally, we discuss the implications of these metabolic alterations for therapeutic strategies, highlighting the potential of targeting energy metabolism to reverse or halt cardiac fibrosis progression. By synthesizing current knowledge and identifying research gaps, this review aims to lay the groundwork for future studies and enhance therapeutic approaches for this challenging condition.

Myocardial infarction (MI) remains a leading cause of mortality, and although reperfusion therapy is essential for myocardial salvage, it often results in ischemia-reperfusion (I/R) injury, which contributes substantially to cardiomyocyte necrosis. Although the mechanisms of cardiomyocyte necrosis remain unclear, we identified ACSS2 as a key regulator in myocardial I/R injury. ACSS2 was upregulated under oxidative stress and I/R conditions. Its knockdown reduced necrosis, while overexpression aggravated it. Mechanistically, nuclear translocation of ACSS2 enhanced H3K9 acetylation and activated necrosis-related genes. In vivo, ACSS2 silencing alleviated myocardial injury and improved cardiac function. These findings reveal that ACSS2 promotes necrosis via nuclear acetyl-CoA production and epigenetic regulation, offering a potential therapeutic target for I/R injury.

This study aimed to evaluate the role of cardiac magnetic resonance (CMR) in updating The Mayo Clinic Hypertrophic Cardiomyopathy (HCM) Genotype Predictor Score. We performed an analysis of 175 HCM patients with an echocardiogram, CMR, and genetic test at the Mayo Clinic (2004 to 2018). Yield of a positive genetic test for the original echocardiogram-based score ranged from 38% (-1 point) to 100% (4 or 5 points), with an AUC of 0.659. Late gadolinium enhancement (LGE) presence was a strong predictor of positive genetic test (p = 0.002) and was added to the original score to create the updated version. The yield of positive genetic test for the updated score ranged from 25% (-1 point) to 100% (5 or 6 points) (p < 0.001), with an AUC of 0.724 and significant increase in diagnostic accuracy (p = 0.03). The updated genotype predictor score had improved accuracy when compared to the prior version.

Myocardial fibrosis (MF) severely impairs the heart structure and function post-myocardial infarction. The study investigated the effectiveness and mechanism of diammonium glycyrrhizinate (DG) on ISO-induced MF. ISO-stimulated mouse cardiac fibroblasts (CFs) were treated with DG to assess the proliferation, inflammation, and fibrosis markers (α-SMA, collagen, TGF-β1, Smad3). The MF model was induced in mice by administering ISO, followed by a 4-week treatment with DG (60 mg/kg/day). Cardiac function was measured using echocardiography, and histology and molecular analyses were performed. DG significantly suppressed the CF proliferation and reduced the expression of fibrotic markers. In ISO-treated mice, DG improved the cardiac function and attenuated the upregulated fibrosis markers. Molecular analysis revealed DG suppressed the TGF-β1/Smad3 pathway activation. The antifibrotic effect was enhanced when combined with STAT3 inhibition. DG effectively alleviates ISO-induced myocardial fibrosis dysfunction by inhibiting the STAT3/Smad3 signaling pathway, demonstrating its potential as a treatment for cardiac fibrosis.

Atherosclerosis remains a leading cause of cardiovascular disease and mortality worldwide, despite advancements in statin therapies. Here, we aimed to identify potential anti-atherosclerosis drugs by an integrated approach combining network medicine-based prediction with empirical validation. Among the top drugs predicted by the preferred algorithm, mesalazine─a drug traditionally used to treat inflammatory bowel disease, was selected for in vivo validation in ApoE^-/- mouse model of atherosclerosis. After an 8-week treatment period, mesalazine significantly inhibited atherosclerosis progression by reducing total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, it decreased the plaque area and hepatic steatosis. Gene expression analysis via RT-qPCR revealed that mesalazine downregulated key genes associated with atherosclerosis. These findings highlight the potential of mesalazine as a repurposed anti-atherosclerosis drug and offer novel insights into drug screening for atherosclerosis treatment.

In-stent restenosis (ISR) is the leading cause of revascularization failure, occurring in up to 10% of patients within 10 years after drug-eluting stent (DES) implantation, and is associated with increased mortality and rehospitalization. Guideline-writing authorities recommend DES over drug-coated balloons (DCB) for ISR treatment. However, this indication is mainly based on trials that did not incorporate intravascular imaging. Recent findings suggest that optical coherence tomography (OCT) patterns in ISR may influence treatment outcomes. The ISAR-DESIRE 5 trial is a randomized study to evaluate whether OCT-defined ISR tissue morphology affects treatment with DES versus DCB. 376 patients with ISR will be stratified by OCT pattern (homogeneous vs. non-homogeneous) and randomized 1:1 to DES or DCB. The trial is powered to detect an interaction between OCT pattern and treatment modality on the 24-month incidence of major adverse cardiac events and represents a step toward establishing a more individualized approach to ISR management.Trial registration (ClinicalTrials.gov): NCT05544864.

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.