Melanocyte proliferation gene 1 regulated metabolic reprogramming in acute myocardial infarction based on the AMPK/mTOR pathway.

MicroRNA-132-3p ameliorates sepsis-induced myocardial injury by suppressing the MyD88/NF-κB pathway

The adult myocardium couples extreme metabolic demand with a finely tuned coronary microvasculature. Continuous, high-work output is sustained by dense capillary networks, short diffusion distances and dominant reliance on mitochondrial oxidative phosphorylation. By contrast, current cardiac tissue engineering platforms, including scaffold-free myocardial constructs, have achieved robust contraction and basic drug responsiveness but remain constrained by fetal-like cardiomyocyte metabolism and incomplete vascular integration. As pluripotent stem cell-derived cardiomyocytes are driven toward more adult-like phenotypes using metabolic maturation strategies-such as substrate switching from glycolysis to fatty acid oxidation-oxygen consumption rises sharply, exposing the limitations of diffusion-limited culture and underspecified vascular design. This Review proposes integrative circulatory engineering as a framework in which metabolic maturation, vascular architecture and perfusion are co-designed rather than optimized in isolation. Scaffold-free myocardial tissues are highlighted as a particularly suitable platform, enabling close cell-cell contact, self-organized microvascular networks and dynamic remodeling of extracellular matrix. We examine how cell type composition, paracrine crosstalk, matrix mechanics and spatial patterning can be orchestrated to align metabolic demand with vascular supply. Perfusion bioreactors are treated as active components of the engineered circulation, providing controlled oxygen delivery, shear conditioning of endothelial networks, dynamic substrate provision and tunable mechanical loading. The concept is extended to in vitro circulatory units that couple myocardial modules to vascular beds and, in advanced implementations, to other metabolic organs. Finally, translational scenarios, disease modelling opportunities, quality control and computational design are discussed. Together, these elements outline a path toward myocardial tissues that approximate the structural, metabolic and functional complexity required for regenerative therapy and high-fidelity disease modeling.

Divaroside alleviates barium chloride-induced arrhythmia by activating the Nrf2/HO-1 axis to modulate autophagy and calcium homeostasis.

YTHDF2 alleviates diabetic cardiomyopathy by targeting m6A-mediated degradation of lncRNA RMRP and inhibiting NLRP3-dependent pyroptosis.

Inonotus obliquus (Ach. ex Pers.) Pilát aqueous extract alleviates acute cold exposure/rewarming-induced myocardial injury by regulating mitochondrial dynamics via liver kinase B1/adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1 alpha signaling pathway activation.

ACSL6 alleviates myocardial hypertrophy by ameliorating cardiac lipid synthesis and mitochondrial function.

Patients with type 2 diabetes mellitus (T2DM) face increased risk of heart failure after myocardial infarction (MI), despite successful PCI and dual anti-platelet therapy (DAPT), due to coronary microvascular obstruction. This study examined whether DAPTs provide vasculoprotective benefits in injured coronary microvessels, including in the setting of chronic hyperglycaemia. Mice were fed a normal (ND) or high-fat diet (HFD) for 16weeks and treated with vehicle, aspirin plus ticagrelor, clopidogrel, prasugrel or cangrelor, anti-GPIbα antibody, or dabigatran. Intravital imaging assessed platelet, neutrophil, and fibrin presence in the beating heart subjected to ischaemia-reperfusion injury (IRI). Laser speckle contrast imaging evaluated overall ventricular perfusion, and infarct size was determined histologically. IRI increased platelet and neutrophil accumulation in coronary capillaries and reduced perfusion. DAPTs, particularly using prasugrel, and anti-GPIbα reduced platelet numbers but increased neutrophil infiltration. Despite limited perfusion improvement, infarct size decreased. Fibrin deposition was also extensive and contributed to platelet recruitment, as shown using dabigatran. HFD-fed mice demonstrated markedly elevated thromboinflammatory cell accumulation. DAPT with prasugrel reduced platelet and neutrophil presence, but left a significant residual presence of both. Despite perfusion improvements, infarcts remained larger. Our data do not support a simple linear relationship between reduced platelet microthrombi, improved perfusion, and infarct limitation. Whilst early platelet inhibition confers cardioprotection independently of flow recovery in healthy mice, metabolic compromise uncouples microvascular flow from myocardial tissue survival. This may explain the diminished cardioprotective efficacy of DAPTs in patients with T2DM and supports exploring combination vasculoprotective therapies targeting multiple microvascular perturbations.

An overview of recent flexible- and soft-biomaterial applications in myocardial infarction and other cardiovascular diseases.

Astragaloside IV mitigates myocardial ischemia/reperfusion injury by modulating the 14-3-3η/GPX4 axis, reducing mitochondrial dysfunction, ferroptosis, and apoptosis.

Recently, catheters incorporating both contact force (CF) sensing and local impedance (LI) measurement-an indicator of tissue temperature-have become clinically available. The present study aims to evaluate the efficacy of superior vena cava isolation (SVCI) using this catheter and to investigate the characteristics of impedance during the procedure. This retrospective study included 64 patients undergoing initial SVCI using the StablePoint catheter (40 W, CF 10-20 g, 8-10 s). We analyzed the success rate of SVCI and impedance data collected from 1 402 ablation points, with particular attention to the dynamics of LI and generator impedance (GI). First-pass isolation was achieved in all cases without complications such as phrenic nerve or sinus node injury. The LI drop was significantly greater and faster than the GI drop in all segments. The 90% decay time of LI was consistently 5-6 s, suggesting effective lesion formation during the resistive heating phase. LI provides a more reliable and localized indicator of tissue response than GI. The temporal profile of LI supports its utility in guiding safe and effective lesion delivery, particularly in the thin myocardial tissue of the SVC. High-power ablation guided by LI and CF using the StablePoint catheter enables safe and effective SVCI with accurate real-time assessment of lesion quality.

Coronary artery disease (CAD) causes irreversible myocardial dysfunction and progressive heart failure due to loss of contractile function and limited endogenous regenerative capacity. Current therapeutic strategies fail to restore lost myocardium or regenerate damaged cardiac tissue. Identifying dysregulated contractility-related genes may reveal actionable targets for stem cell engineering, iPSC-derived cardiomyocyte design, and tissue regeneration aimed at restoring myocardial contractility and function. Transcriptomic data from the GSE20680 dataset (195 total samples; 87 CAD cases versus 52 healthy controls, N=139; 56 intermediate stenosis subjects used for sensitivity analyses) were analyzed. Functional enrichment was performed with clusterProfiler, and protein-protein interaction (PPI) networks were constructed with STRING/Cytoscape. Protein validation was conducted in peripheral blood mononuclear cells (PBMCs) from 64 angiographically confirmed CAD patients and 55 matched healthy controls by Western blotting, with diagnostic accuracy assessed by receiver operating characteristic (ROC) analysis. Mechanistic studies employed human coronary artery smooth muscle cells (HCASMCs) transduced with lentiviral overexpression vectors or transfected with siRNA constructs targeting selected DEGs; proliferation (colony formation assay) and apoptosis (Annexin V/PI flow cytometry) were evaluated to establish regenerative targeting rationale. Differential expression analysis identified 319 DEGs (226 downregulated, 93 upregulated). Nine myocardial contractility-related genes were prioritized: UQCRQ, COX7C, COX6C, SLC8A1, COX7B, COX7A2, TNNT2, CACNB2, and CACNB1. Protein expression changes in PBMC lysates were directionally consistent with mRNA dysregulation: eight genes were significantly downregulated at the protein level, while COX7B was upregulated (P<0.05). ROC analysis demonstrated robust diagnostic performance (AUC 0.799-0.900). In HCASMCs, correcting dysregulation of the eight downregulated genes (by lentiviral overexpression) suppressed proliferation and enhanced apoptosis, suggesting restoration of contractile phenotype. COX7B exhibited the reverse pattern, supporting its distinct detrimental role. These expression patterns suggest that gene correction in engineered cardiomyocytes could restore contractile function and improve cell survival post-transplantation. This nine-gene contractility-related signature represents a set of CAD-associated biomarkers with plausible links to myocardial excitation-contraction pathways. Our integrated PBMC and HCASMC data suggest that these genes may influence vascular remodeling, and they highlight candidate targets for future regenerative studies, but direct validation in human myocardial tissue and cardiomyocytes will be required before firm conclusions about myocardial contractility or regenerative efficacy can be drawn.

Exercise-primed exosomes in an injectable hydrogel promote myocardial repair via angiogenesis and ferroptosis inhibition.

Synergistic effects of CAR-modified mesenchymal stem cells and MGST1 activation in facilitating myocardial tissue repair post-ischemia-reperfusion injury.

Myocardial ischemia/reperfusion (MI/R) injury may cause serious arrhythmia and even sudden death. Sirtuin 2 (SIRT2) belongs to NAD (+) dependent class III histone deacetylase. The present study explored the potential mechanism of SIRT2 in MI/R injury. A rat model with MI/R injury was established. Differentially expressed genes in myocardial tissues of MI/R-treated rats and sham-operated rats were analyzed by microarray. The AAV9-encapsulated SIRT2 overexpression vector was injected into rats to evaluate the effect of SIRT2 on MI/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R) treatment was used to simulate MI/R injury at a cellular level. SIRT2 overexpression vector was transfected into cardiomyocytes. The expression of forkhead box O3 (FOXO3), a potential transcription factor predicted to bind to SIRT2, was detected in myocardial tissues of modeled rats and OGD/R-treated cardiomyocytes. The effect of FOXO3 on OGD/R-treated cardiomyocytes was confirmed by functional rescue experiments. The expressions of NLRP3 and caspase1 were detected. SIRT2 was downregulated in myocardial tissues of MI/R-treated rats. Overexpression of SIRT2 alleviated MI/R injury in modeled rats and enhanced viability of OGD/R-treated cardiomyocytes. FOXO3 activated SIRT2 transcription and expression. FOXO3 was downregulated in the myocardial tissues of MI/R-treated rats and OGD/R-treated cardiomyocytes. Knockdown of FOXO3 weakened the effects of SIRT2 on MI/R injury. SIRT2 reduced MI/R injury by inhibiting NLPR3/caspase1 inflammasome signaling. FOXO3 activates SIRT2 expression and inhibits NLPR3 inflammasome signaling pathway, thus alleviating MI/R injury. This study may offer a novel molecular target for the management of MI/R injury.

Septic cardiomyopathy (SCM) is a severe complication of sepsis. The therapeutic potential of Ginsenoside Rh4 (Rh4) in SCM remains unclear. This study aimed to investigate the effects and mechanisms of Rh4 on SCM using both in vivo and in vitro approaches. In the in vivo experiments, Rh4 significantly reduced the mortality rate in SCM mice, improved ejection fraction and diastolic function, and protected myocardial cell mitochondria, thereby alleviating myocardial cell injury. Transcriptomic sequencing, ELISA, and PCR results suggested that Rh4 reduced inflammatory cytokines in myocardial tissues, likely through the inhibition of the NF-κB signaling pathway. This effect was associated with a reduction in pro-inflammatory M1 macrophages and an increase in the proportion of reparative M2 macrophages. Additionally, Rh4 alleviated myocardial cell apoptosis and attenuated myocardial fibrosis at later stages. In vitro, we found that Rh4 reduced LPS-induced macrophage polarization and promoted the polarization of macrophages into anti-inflammatory M2 macrophages. Moreover, flow cytometry analysis revealed that Rh4 decreased reactive oxygen species (ROS) production in HL-1 cardiomyocytes, with the mechanism linked to the activation of the Keap1/Nrf2/HO-1 signaling pathway. Finally, Rh4 treatment significantly inhibited the pro-apoptotic effects of LPS on HL-1 cells. In conclusion, Rh4 improves heart function by reducing macrophage polarization and ROS generation, protecting myocardial cell mitochondria, and reducing myocardial cell apoptosis.

Machine Learning-Based Study on Xin-Pi Simultaneous Treatment Formula via Drug Nanodelivery Systems Regulating Macrophage Polarization and TEAD2/PKM2 Synergistic Repair Strategy in Myocarditis.

Radiation‐induced heart disease (RIHD) is a myocardial lesion caused by radiation exposure, and its pathogenesis is closely associated with oxidative stress. ATOX1 has been demonstrated to regulate oxidative stress, but its mechanism in RIHD remains unclear. We analyzed ATOX1 expression (Western blot [WB], RT‐PCR), cardiomyocyte proliferation (MTT, IF), apoptosis (TUNEL), AMPK signaling (WB, IF), and mitochondrial function (reactive oxygen species [ROS], mPTP, JC‐1) in vitro. A thoracic irradiation model was used in cardiomyocyte‐specific ATOX1 knockout mice. Tissue analysis included IHC for ATOX1, KI‐67, p‐AMPK, and assessment of myocardial injury (ELISA, RT‐PCR, and Masson's staining). Irradiation significantly reduced cardiomyocyte proliferation and increased apoptosis. ATOX1 levels plummeted in irradiated cardiomyocytes, accompanied by mitochondrial ROS surges and disrupted integrity. Irradiation suppressed the AMPK/NRF2 axis, an effect reversed by ATOX1 overexpression. In mice, ATOX1 knockout exacerbated radiation‐induced myocardial tissue damage. ATOX1 mitigates irradiation‐induced cardiac damage by promoting mitochondrial and redox homeostasis in cardiomyocytes through AMPK/NRF2 pathway activation.

Myocardial ischemia-reperfusion (MI/R) injury significantly limits the clinical benefits of coronary reperfusion therapy. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in myocardial ischemia-reperfusion (I/R) injury. Liproxstatin-1 (Lip-1) is a potent ferroptosis inhibitor, but its dynamic, dose-dependent effects on key molecular pathways and pathological hallmarks in the heart remain incompletely characterized. To systematically investigate the dose- and time-dependent cardioprotective effects of Lip-1 against myocardial I/R injury, with a focus on the NRF2/GPX4 pathway, iron deposition, and lysosomal integrity. Ninety Wistar rats were randomly allocated to 15 experimental groups (n = 6 per group): Normal (no surgery), Sham (thoracotomy without ischemia), I/R model, and I/R + Lip-1 treatment groups. Lip-1 was administered intravenously at doses of 1, 3, or 5mg/kg at 0, 24, 48, and 72h post-reperfusion initiation, with myocardial tissue and blood samples harvested 6h after each injection. Cardiac function was assessed by echocardiography. Myocardial infarct size was determined by Evans Blue/TTC double staining. Serum levels of CK-MB and LDH were measured as markers of myocardial injury. Analyses included Western blot for NRF2 and GPX4 expression, Prussian blue staining for iron deposition quantification, and immunofluorescence for LAMP1 localization and intensity. Statistical analysis was performed using two-way ANOVA with Tukey's post hoc test for Lip-1 treatment groups, and t-tests or one-way ANOVA for model validation comparisons. Compared to Sham, I/R injury significantly decreased LVEF, increased infarct size, and elevated CK-MB and LDH levels (all P < 0.0001), confirming successful model establishment. It also downregulated GPX4 expression, induced severe iron deposition, and reduced LAMP1 levels, while triggering an adaptive upregulation of NRF2. Lip-1 treatment produced dose- and time-dependent protection across all measured endpoints. It improved cardiac function, reduced infarct size, and attenuated CK-MB and LDH release, with significant dose×time interactions for infarct size (F(6,60) = 8.338, P < 0.0001), CK-MB (F(6,60) = 6.467, P < 0.0001), and LDH (F(6,60) = 9.021, P < 0.0001). It dynamically modulated the NRF2/GPX4 axis, with peak GPX4 expression observed following the 48-hour administration (sampled at 54h post-reperfusion). Lip-1 progressively reduced iron deposition, with maximal effect observed after the 72-hour administration (sampled at 78h post-reperfusion), and rescued LAMP1 downregulation in later sampling points. Statistical analysis revealed significant dose×time interactions for NRF2 (F(6,60) = 200.8, p < 0.0001), GPX4 (F(6,60) = 34.84, p < 0.0001), and iron deposition. High-dose Lip-1 (5mg/kg) demonstrated superior and sustained efficacy across all parameters. Lip-1 confers multi-faceted cardioprotection against I/R injury through sequential mechanisms involving early potentiation of the NRF2/GPX4 antioxidant defense, progressive attenuation of pathological iron accumulation, and restoration of lysosomal membrane integrity. The strict dose and temporal dependency of these effects provide critical insights for optimizing ferroptosis-targeted therapeutic strategies in ischemic heart disease.

The implementation of photon-counting (PCD) CT has led to substantial technologic improvements over conventional energy-integrated detector (EID) CT. These advances include better spatial and contrast resolution, intrinsic spectral information, and potential for reductions in radiation doses and contrast media volumes. Since the clinical introduction of PCD CT, numerous studies have been performed to investigate the advantages and potential impact brought by this new technology for various clinical scenarios with respect to cardiothoracic imaging. For example, PCD CT offers improved visualization of pulmonary and cardiac anatomy and allows dose reduction in the assessment of pulmonary vasculature, nodules, emphysema, and interstitial lung diseases. PCD CT also improves visualization of coronary plaque and stents, provides more accurate assessment of coronary stenoses, and facilitates myocardial tissue characterization. The faster data acquisition enabled by PCD CT additionally aids cardiothoracic evaluation in pediatric and/or dyspneic patients. This AJR Expert Panel Narrative Review explores these state-of-the art cardiothoracic applications of PCD CT considering supporting evidence, technical features, protocols, and areas of greatest potential clinical benefit. Ongoing implementation challenges and remaining research priorities that warrant attention to support the integration of PCD CT into standard cardiothoracic imaging practice are highlighted.