Shichun Shen

Fibrosis is a critical component of ventricular remodelling after myocardial ischemia, and the activation and expansion of cardiac fibroblasts represent key drivers of this process. Our previous work identified S100A9‐dependent macrophage‐to‐myofibroblast transition (MMT) as a newly recognized source of myofibroblasts in the post‐MIR heart. However, the mechanisms by which S100A9 regulates MMT remain incompletely understood. Here, using multiple genetically engineered mouse models, MIR and MI model, and in vitro multicellular co‐culture systems, we investigated the role of S100A9 in regulating fibroblast‐derived migrasome release during MMT. We found that macrophage‐derived S100A9 promotes mitochondrial dysfunction and migrasome release in cardiac fibroblasts through TLR4/PGC1α signalling following MIR. These fibroblast‐derived migrasomes, in turn, activate integrin/Src signalling in macrophages, triggering MMT and accelerating cardiac fibrosis. Importantly, we delineate how macrophage‐derived S100A9 orchestrates crosstalk between fibroblasts and immune cells and identify migrasome‐mediated activation of MMT as a previously unrecognized mechanism driving post‐MIR fibrotic remodelling. Our findings suggest that targeting S100A9‐induced migrasome release and downstream MMT signalling may represent a promising therapeutic strategy to mitigate pathological cardiac fibrosis.

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by pulmonary vasoconstriction and remodeling. This study seeks to delineate the role of macrophage‐derived S100 calcium‐binding protein A9 (S100A9) in inducing inflammatory responses mediated by mitochondria‐endoplasmic reticulum (ER) interactions in pulmonary arterial endothelial cells (ECs) during PAH pathogenesis. Both in vivo and in vitro findings consistently revealed that macrophage‐derived S100A9 significantly exacerbated EC injury. Either deletion of S100a9 gene or S100A9 inhibitor restricted pathological progression in PAH mice significantly. S100A9 activates the toll‐like receptor 4 (TLR4)/p38 mitogen‐activated protein kinase (TLR4/p38) pathway in ECs, leading to upregulation of signal‐transducing adaptor protein 2 (STAP2), which subsequently interacts with leucine‐rich repeat kinase 2 to enhance ER‐mitochondrial contact, thereby activating the NOD‐like receptor family pyrin domain containing 3 inflammasome signaling cascade. Targeting STAP2 or inhibiting mitochondria‐ER contact effectively alleviated S100A9‐induced EC injury and PAH progression. This study demonstrates that macrophage‐derived S100A9 promotes pulmonary arterial EC injury via TLR4/STAP2‐mediated mitochondrial–ER interactions, thereby exacerbating PAH progression. Genetic or molecular interventions targeting S100A9 exhibit promising therapeutic potential for ameliorating PAH.

Heart failure (HF) continues to be a leading cause of death and disability globally, with an estimated annual prevalence of over 56 million patients and a projected significant increase in occurrence. Although drug treatments based on existing guidelines can enhance the clinical prognosis for patients with HF, the five‐year survival rate remains below 50%. This underscores the critical need for early detection and effective strategies to prevent and manage the progression of HF. Present screening approaches, encompassing individual biomarkers and imaging techniques, exhibit shortcomings in identifying subclinical or incipient‐stage diseases. This review amalgamates the most recent advancements in HF screening, specifically highlighting novel biomarkers that correspond to various pathways involved in cardiac remodeling, inflammation, neurohormones, and emerging pathophysiological pathways. Several emerging biomarkers, notably sST2 and GDF‐15, demonstrate strong potential for inclusion in future clinical guidelines, enhancing early risk stratification and personalized screening. Artificial intelligence‐driven approaches, integrating electrocardiograms, wearable devices, and analysis of medical images using machine learning and multimodal data, represent a promising strategy for improving early risk identification. Nevertheless, it is imperative for researchers to systematically address enduring challenges. These challenges encompass analytical variability in machine learning data, the absence of multicenter clinical trial data, constraints in hardware deployment, and biases prevalent in resource‐limited settings. Future research endeavors should prioritize the integration of multi‐omics technologies, thereby enhancing the precision of biomarkers. This would enhance biomarker accuracy, facilitate dynamic risk stratification for HF, and guarantee equitable global implementation. Combining evidence‐based methodologies with technological innovation will be fundamental to developing scalable screening tools. Implementing such a stepwise integrated screening framework will allow clinicians to optimize therapeutic timing and improve survival outcomes in HF management.

Emerging evidence highlights the central role of gut microbiota in maintaining physiological homeostasis within the host. Disruptions in gut microbiota can destabilize systemic metabolism and inflammation, driving the onset and progression of cardiometabolic diseases. In heart failure (HF), intestinal dysfunction may induce the release of endotoxins and metabolites, leading to dysbiosis and exacerbating HF through the gut–heart axis. Understanding the relationship between gut microbiota and HF offers critical insights into disease mechanisms and therapeutic opportunities. Current research highlights promising potential to improve patient outcomes by restoring microbiota balance. In this review, we summarize the current studies in understanding the gut microbiota–HF connection and discuss avenues for future investigation.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with a high fatality rate. Cardiac injury in SFTS patients is a major concern. This study aimed to evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with novel Bunyavirus. Cardiac injury was defined as the presence of any of the following abnormalities: (1) blood levels of cardiac biomarkers (creatine kinase‐MB, troponin‐I, B‐type natriuretic peptide or N‐terminal pro‐B‐type natriuretic peptide); (2) new abnormalities in electrocardiography. The 203 SFTS patients were included in the final analysis. The proportion of SFTS patients developing cardiac injury during hospitalization was 71.4% (145/203). Compared with the uninjured group, the cardiac injury group had the severity of cardiac injury was underscored by higher median hospital costs (31420 vs. 12911, p < 0.001), higher proportion of intensive care units admissions (13.1% vs. 3.4%, p = 0.041), and higher hospital mortality rate (33.8% vs. 6.9%, p < 0.001). Multivariable‐adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality during hospitalization (hazards ratio, 7.349; 95% CI: 2.352–22.960). Cardiac injury is common among hospitalized SFTS patients, and it is associated with higher risk of mortality.