Macrophage-based therapeutic approaches for cardiovascular diseases

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: 119(1), P. 1 - 33

Published: Jan. 3, 2024

Despite the advances in treatment options, cardiovascular disease (CVDs) remains leading cause of death over world. Chronic inflammatory response and irreversible fibrosis are main underlying pathophysiological causes progression CVDs. In recent decades, cardiac macrophages have been recognized as regulatory players development these complex conditions. Numerous approaches aimed at devised, to novel prospects for therapeutic interventions. Our review covers advancements macrophage-centric plans various pathologic conditions examines potential consequences obstacles employing macrophage-targeted techniques diseases.

Language: Английский

---

Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

---

The RNA-binding protein landscapes differ between mammalian organs and cultured cells

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 12, 2023

Abstract System-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo enhanced RNA interactome capture (eRIC) characterize three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) these had formerly not been identified cells, with 100 being metabolic enzymes. Remarkably, RBP activity differs between independent abundance, suggesting organ-specific levels control. Similarly, identify systematic differences binding animal and pervasive enzymes intermediary metabolism points tightly knit connections gene expression metabolism, displays particular enrichment for that use nucleotide cofactors. We generically applicable refinement eRIC technology provide instructive resource intact organs, including brain.

Language: Английский

---

Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 23, 2023

Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In present study, we explored correlation between AFP regulation function possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) monocytes from healthy donors were used to analyze effect on macrophages’ phenotype phagocytosis. THP-1 human donor-derived polarized into M0 macrophages induced by phorbol ester (PMA), M1 lipopolysaccharide(LPS) interferon-γ(IFN-γ). Interleukin-4(IL-4) interleukin-13(IL-13) induce M2 macrophages. Tumor-derived AFP(tAFP) stimulated inhibited phagocytize HCC cells. The promoting inhibiting may be involved activating PI3K/Akt signaling pathway. could also enhanced migration ability apoptosis when co-cultured with M1-like pivotal cytokine that inhibits

Language: Английский

---

Redox regulation of macrophages

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103123 - 103123

Published: March 12, 2024

Redox signaling, a mode of signal transduction that involves the transfer electrons from nucleophilic to electrophilic molecule, has emerged as an essential regulator inflammatory macrophages. reactions are driven by reactive oxygen/nitrogen species (ROS and RNS) redox-sensitive metabolites such fumarate itaconate which can post-translationally modify specific cysteine residues in target proteins. In past decade our understanding how ROS, RNS, control macrophage function expanded dramatically. this review, we discuss latest evidence regulate is dysregulated with disease. We highlight key tools assess redox signaling important questions remain.

Language: Английский

---

Near-infrared light responsive gold nanoparticles coating endows polyetheretherketone with enhanced osseointegration and antibacterial properties

Materials Today Bio, Journal Year: 2024, Volume and Issue: 25, P. 100982 - 100982

Published: Feb. 1, 2024

Polyetheretherketone (PEEK) is considered as a promising dental implant material owing to its excellent physicochemical and mechanical properties. However, wide range of applications limited by biologically inert nature. In this study, near-infrared (NIR) light responsive bioactive coating with gold nanoparticles (AuNPs) metronidazole adhered the PEEK surface via dopamine polymerization. Compared pure PEEK, hydrophilicity treated was significantly improved. addition, under NIR light, exhibited photothermal conversion effect, antibiotic can be released from coating. This improved antibacterial properties materials. Moreover, more conducive early adhesion bone mesenchymal stem cells. The results in vitro vivo osteogenic activity studies showed that promoted osseointegration implants, irradiation further ability implants. Through RNA sequencing data mining, potential underlying mechanism promoting formation AuNPs combined interpreted. summary, developed may treatment strategy endows

Language: Английский

---

Development of a CD163-Targeted PET Radiotracer That Images Resident Macrophages in Atherosclerosis

Journal of Nuclear Medicine, Journal Year: 2024, Volume and Issue: 65(5), P. 775 - 780

Published: March 28, 2024

Tissue-resident macrophages are complementary to proinflammatory promote the progression of atherosclerosis. The noninvasive detection their presence and dynamic variation will be important understanding role in pathogenesis goal this study was develop a targeted PET radiotracer for imaging CD163-positive (CD163+) multiple mouse atherosclerosis models assess potential CD163 as biomarker humans. Methods: CD163-binding peptide identified using phage display conjugated with NODAGA chelator ⁶⁴Cu radiolabeling ([⁶⁴Cu]Cu-ICT-01). CD163-overexpressing U87 cells were used measure binding affinity [⁶⁴Cu]Cu-ICT-01. Biodistribution studies performed on wild-type C57BL/6 mice at time points after tail vein injection. sensitivity specificity [⁶⁴Cu]Cu-ICT-01 CD163+ upregulated surface atherosclerotic plaques assessed models. Immunostaining, flow cytometry, single-cell RNA sequencing characterize expression tissue-resident macrophages. Human carotid resident test Results: showed high cells. biodistribution rapid blood renal clearance low retention all major organs 1, 2, 4 h In an ApoE^−/− model, demonstrated sensitive specific capability tracking lesions; these findings further confirmed Ldlr^−/− PCSK9 Immunostaining elevated across plaques. Flow cytometry tissue characterization lesions, ex vivo autoradiography revealed human CD163. Conclusion: This work reported development indicated vulnerable warrant investigation translational settings.

Language: Английский

---

Prediction of six macrophage phenotypes and their IL-10 content based on single-cell morphology using artificial intelligence

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Introduction The last decade has led to rapid developments and increased usage of computational tools at the single-cell level. However, our knowledge remains limited in how extracellular cues alter quantitative macrophage morphology such morphological changes can be used predict phenotype as well cytokine content Methods Using an artificial intelligence (AI) based approach, this study determined whether (i) accurate classification (ii) prediction intracellular IL-10 level was possible, using only features predictors for AI. a panel shape descriptors, assessed image-based original synthetic data two different datasets which CD14+ monocyte-derived macrophages generated from human peripheral blood monocytes were initially primed with GM-CSF or M-CSF followed by polarization specific stimuli presence/absence continuous M-CSF. Specifically, M0, M1 (GM-CSF-M1, TNFα/IFNγ-M1, GM-CSF/TNFα/IFNγ-M1) M2 (M-CSF-M2, IL-4-M2a, M-CSF/IL-4-M2a, IL-10-M2c, M-CSF/IL-10-M2c) examined. Results Phenotypes confirmed ELISA immunostaining CD markers. Variations techniques significantly changed multiple features, demonstrating that is highly sensitive, dynamic marker phenotype. data, cell alone yielded accuracy 93% 6 phenotypes (with M-CSF). A similarly high 95% reached (discontinuous M-CSF) measured time point. These comparably accuracies clearly validated here chosen AI-based approach. Quantitative also allowed data. Discussion Thus, machine learning morphology-based not classified but M2a M2c subtypes (iii) predicted among six phenotypes. This simple approach general strategy phenotyping any producing cell, help improve understanding biology

Language: Английский

---

Stimuli‐Mediated Macrophage Switching, Unraveling the Dynamics at the Nanoplatforms–Macrophage Interface

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(20)

Published: April 19, 2024

Abstract Macrophages play an essential role in immunotherapy and tissue regeneration owing to their remarkable plasticity diverse functions. Recent bioengineering developments have focused on using external physical stimuli such as electric magnetic fields, temperature, compressive stress, among others, micro/nanostructures induce macrophage polarization, thereby increasing therapeutic potential. However, it is difficult find a concise review of the interaction between stimuli, advanced micro/nanostructures, polarization. This examines present research stimuli‐induced polarization micro/nanoplatforms, emphasizing synergistic fabricated structure stimulation for regeneration. A overview advancements investigating impact including forces, fluid shear photothermal multiple stimulations macrophages within complex engineered structures, provided. The prospective implications these strategies regenerative medicine immunotherapeutic approaches are highlighted. will aid creating stimuli‐responsive platforms immunomodulation

Language: Английский

---

Stimulus-response signaling dynamics characterize macrophage polarization states

Cell Systems, Journal Year: 2024, Volume and Issue: 15(6), P. 563 - 577.e6

Published: June 1, 2024

The functional state of cells is dependent on their microenvironmental context. Prior studies described how polarizing cytokines alter macrophage transcriptomes and epigenomes. Here, we characterized the responses 6 differentially polarized populations by measuring dynamics transcription factor nuclear κB (NF-κB) in response to 8 stimuli. resulting dataset single-cell NF-κB trajectories was analyzed three approaches: (1) machine learning time-series data revealed losses stimulus distinguishability with polarization, reflecting canalized effector functions. (2) Informative trajectory features driving ("signaling codons") were identified used for mapping a cell landscape that could then locate macrophages conditioned an unrelated condition. (3) Kinetic parameters, inferred using mechanistic network model, provided alternative states correctly predicted biochemical findings. Together, this work demonstrates single analyte's dynamic may distinguish molecular underlying them. A record paper's transparent peer review process included supplemental information.

Language: Английский

---