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Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis-associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Atherosclerosis (AS), with associated risk of stroke or cerebrovascular disease, is one of the most common causes of death globally. It has been well established that tripartite motif‐containing protein 7 Tripartite Motif‐containing 7 (Trim7), as an E3 ubiquitin protein ligase, is involved in protein ubiquitination and thus regulating cellular proliferation. Moreover, TRIM7 is upregulated in advanced carotid AS. However, the detailed mechanism of TRIM7 on regulation of AS remains unclear. In the present study, we firstly discovered that TRIM7 expression was robustly induced in platelet‐derived growth factor type BB‐treated vascular smooth muscle cells (VSMCs) and human atherosclerotic plaques. Functional approaches established that knockdown of TRIM7 inhibited proliferation and migration of VSMCs, as well as arrested the cell cycle at G1‐S, thus suppressing AS progression. Our results also identified that c‐Jun/activator protein 1 (AP‐1) signaling pathway was activated by TRIM7. Moreover, gain‐ and loss‐of‐function studies revealed that TRIM7 could promote proliferation and migration of VSMCs via activation of c‐Jun/AP‐1 signaling pathway. Finally, by using atherogenic apolipoprotein E‐deficient (apoE–/–) C57BL/6 mice with high‐fat diet AS model, we demonstrated that interference of TRIM7 could effectively mitigate in vivo AS via inactivation of c‐Jun/AP‐1 signaling pathway. In general, activation of c‐Jun/AP‐1 signaling pathway via TRIM7 could be an important mechanism in AS progression, thus shedding light on the development of novel therapeutics to the treatment of the disease. [ABSTRACT FROM AUTHOR]

As heterogeneous immune cells, macrophages mount effective responses to various internal and external changes during disease progression. Macrophage polarization, rather than macrophage heterogenization, is often used to describe the functional differences between macrophages. While macrophage polarization partially contributes to heterogeneity, it does not completely explain the concept of macrophage heterogeneity. At the same time, there are abundant and sophisticated endogenous and exogenous substances that can affect macrophage heterogeneity. While the research on endogenous factors has been systematically reviewed, the findings on exogenous factors have not been well summarized. Hence, we reviewed the characteristics and inducing factors of heterogeneous macrophages to reveal their functional plasticity as well as their targeting manoeuvreability. In the process of constructing and analysing a network organized by disease‐related cells and molecules, paying more attention to heterogeneous macrophages as mediators of this network may help to explore a novel entry point for early prevention of and intervention in disease. [ABSTRACT FROM AUTHOR]

Macrophages display significant phenotypic heterogeneity. Two growth factors, macrophage colony-stimulating factor and chemokine (C-X-C motif) ligand 4, drive terminal differentiation of monocytes to M0 and M4 macrophages respectively. Compared to M0 macrophages, M4 cells have a unique transcriptome, with expression of surface markers such as S100A8, mannose receptor CD206 and matrix metalloproteinase 7. M4 macrophages did not express CD163, a scavenger receptor for haemoglobin/haptoglobin complex. Depending on the stimuli, M0 macrophages could polarize towards the proinflammatory M1 subset by treatment with lipopolysaccharide or interferon-γ. These macrophages produce a range of proinflammatory cytokines, nitric oxide, reactive oxygen species and exhibit high chemotactic and phagocytic activity. The alternative M2 type could be induced from M0 macrophage by stimulation with interleukin ( IL)-4. M2 macrophages express high levels of CD206 and produce anti-inflammatory cytokines IL-10 and transforming growth factor-β. M1, M2 and M4 macrophages could be found in atherosclerotic plaques. In the plaque, macrophages are subjected to the intensive influence not only by cytokines and chemokines but also with bioactive lipids such as cholesterol and oxidized phospholipids. Oxidized phospholipids induce a distinct Mox phenotype in murine macrophages that express a unique panel of antioxidant enzymes under control of the redox-regulated transcription factor Klf2, resistant to lipid accumulation. In unstable human lesions, atheroprotective M(Hb) and HA-mac macrophage subsets could be found. These two subsets are induced by the haemoglobin/haptoglobin complex, highly express haeme oxygenase 1 and CD163, and are implicated in clearance of haemoglobin and erythrocyte remnants. In atherogenesis, the macrophage phenotype is plastic and could therefore be switched to proinflammatory ( i.e. proatherogenic) and anti-inflammatory ( i.e. atheroprotective). The aim of this review was to characterize changes in macrophage transcriptome in atherosclerosis and discuss key markers that characterize different phenotypes of macrophages present in atherosclerotic lesions. [ABSTRACT FROM AUTHOR]