Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved. Here, we showed that adoptive transfer of Bregs ameliorated ventricular remodeling in a murine MI model, as demonstrated by improved cardiac function, decreased scar size and attenuated interstitial fibrosis without changing the survival rate. Reduced Ly6C^hi monocyte infiltration was found in the hearts of the Breg-transferred mice, while the infiltration of Ly6C^lo monocytes was not affected. In addition, the replenishment of Bregs had no effect on the myocardial accumulation of T cells or neutrophils. Mechanistically, Bregs reduced the expression of C–C motif chemokine receptor 2 (CCR2) in monocytes, which inhibited proinflammatory monocyte recruitment to the heart from the peripheral blood and mobilization from the bone marrow. Breg-mediated protection against MI was abrogated by treatment with an interleukin 10 (IL-10) antibody. Finally, IL-10 neutralization reversed the effect of Bregs on monocyte migration and CCR2 expression. The present study suggests a therapeutic value of Bregs in limiting ventricular remodeling after MI through decreasing CCR2-mediated monocyte recruitment and mobilization.

Myocardial infarction (MI) is defined as sudden ischemic death of myocardial tissue. Amphiregulin (Areg) regulates cell survival and is crucial for the healing of tissues after damage. However, the functions and mechanisms of Areg after MI remain unclear. Here, we aimed to investigate Areg's impact on myocardial remodeling. Mice model of MI was constructed and Areg ^−/− mice were used. Expression of Areg was analyzed using western blotting, RT–qPCR, flow cytometry, and immunofluorescence staining. Echocardiographic analysis, Masson's trichrome, and triphenyltetrazolium chloride staining were used to assess cardiac function and structure. RNA sequencing was used for unbiased analysis. Apoptosis and autophagy were determined by western blotting, TUNEL staining, electron microscopy, and mRFP‐GFP‐LC3 lentivirus. Lysosomal acidity was determined by Lysotracker staining. Areg was elevated in the infarct border zone after MI. It was mostly secreted by macrophages. Areg deficiency aggravated adverse ventricular remodeling, as reflected by worsening cardiac function, a lower survival rate, increased scar size, and interstitial fibrosis. RNA sequencing analyses showed that Areg related to the epidermal growth factor receptor (EGFR), phosphoinositide 3‐kinase/protein kinase B (PI3K‐Akt), mammalian target of rapamycin (mTOR) signaling pathways, V‐ATPase and lysosome pathways. Mechanistically, Areg exerts beneficial effects via increasing lysosomal acidity to promote autophagosome clearance, and activating the EGFR/PI3K/Akt/mTOR signaling pathway, subsequently inhibiting excessive autophagosome formation and apoptosis in cardiomyocytes. This study provides a novel evidence for the role of Areg in inhibiting ventricular remodeling after MI by regulating autophagy and apoptosis and identifies Areg as a potential therapeutic target in ventricular remodeling after MI.

As immunoregulatory cells, regulatory T cells (Tregs) play pivotal roles in maintaining immune tolerance and preventing autoimmunity. However, Tregs exhibit distinct functions across different diseases. In cancer, Tregs are most likely to suppress antitumor immune responses and promote tumor immune evasion, whereas in inflammatory diseases, functionally competent Tregs mitigate excessive immune activation and facilitate tissue repair. Notably, dysfunctional Tregs lead to persistent inflammation and progression to chronic disease. Therefore, targeting Tregs has emerged as an attractive immunotherapeutic strategy for both cancer and inflammatory disorders. Recent studies have shown that Tregs exhibit instability and plasticity under specific conditions, allowing them to shift between functional and dysfunctional states. A comprehensive understanding of the dynamic changes in Tregs and their regulatory mechanisms in diverse pathological contexts is highly important. In this review, we summarize the dual roles of Tregs in cancer and various inflammatory diseases. We explore the signaling pathways and molecular mechanisms underlying their biological characteristics, with a particular focus on how microenvironmental cues shape Treg behavior. Additionally, we discuss recent advances in Treg-targeted therapies in these disease contexts. Overall, this review greatly advances our understanding of the roles of Tregs in cancer and inflammation and helps inform the development of more precise and effective therapeutic strategies.

Atherosclerosis, the primary cause of coronary artery disease (CAD), remains a leading global cause of mortality. It is characterized by the accumulation of cholesterol-rich plaques and inflammation, which narrow the coronary arteries and increase the risk of rupture. To elucidate this complex biological process and improve therapeutic strategies, CAD has been extensively explored from an epigenetic perspective over the past two decades. Epigenetics is a field investigating heritable alterations in gene expression without DNA sequence changes, such as DNA methylation, histone modifications, and non-coding RNAs. Increasing evidence has indicated that the development of CAD is significantly influenced by epigenetic changes. Meanwhile, the impact of epigenetics in CAD is now transitioning from pathophysiology to therapeutics. Focusing on the key epigenetic enzymes and their target genes will help to facilitate the diagnosis and treatment of CAD. This review synthesizes novel epigenetic insights into CAD, addressing the pathological processes, key molecular mechanisms, and potential biomarkers. Furthermore, we discuss emerging therapeutic strategies targeting epigenetic pathways. By focusing on pivotal enzymes and their associated genes, this work aims to advance CAD diagnostics and interventions.