Journal of Cardiovascular Translational Research最新文献

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.

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.