Macrophages and cardiac lesion in zebrafish: what can single-cell RNA sequencing reveal?

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 11, 2025

Unlike mammals, zebrafish can regenerate their heart after cardiac insult. There are several ways to perform injury in zebrafish, but cryoinjury most closely resembles human myocardial infarction (MI). Studies demonstrated that macrophages essential cells from the beginning later stages of throughout regenerative process zebrafish. These have phenotypic plasticity; hence, overly sensitive techniques, such as single-cell RNA sequencing (scRNAseq), for uncovering phenotype needed regeneration, inflammatory profile initiation scar resolution. This technique enables individual cells, thus generating clusters with similar gene expression and allowing study a particular cell population. Therefore, this review, we focused on discussing data obtained by scRNAseq context injury. We found 1 7 days post-injury (dpi), present reparative functions either or ventricular resection. At 14 dpi, there were differences between models, especially cytokines, studies time points understand enrolls collagen resorption dynamic.

Language: Английский

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Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 25, 2024

Background Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages considered be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied many medical fields as active participants immunity, cooperation between platelets is essential. this context, aim review compile current evidence regarding effects on phenotype functions identify advantages shortcomings for feasible future clinical applications. Methods A total 669 articles were identified during systematic literature search performed PubMed Web Science databases. Results 27 met inclusion criteria. Based published findings, may play important role inducing a dynamic M1/M2 balance promoting timely M1-M2 shift. However, differences procedures polarization occasional lack information, makes reproducibility comparison results extremely challenging. Furthermore, understanding those derived from animal models, taking into account peculiarities tissue resident ontogeny seem essential design new strategies. Conclusion Research combination provides relevant information function mechanisms response.

Language: Английский

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Macrophage‐mediated heart repair and remodeling: A promising therapeutic target for post‐myocardial infarction heart failure

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 239(11)

Published: July 16, 2024

Heart failure (HF) remains prevalent in patients who survived myocardial infarction (MI). Despite the accessibility of primary percutaneous coronary intervention and medications that alleviate ventricular remodeling with functional improvement, there is an urgent need for clinicians basic scientists to further reveal mechanisms behind post-MI HF as well investigate earlier more efficient treatment after MI. Growing numbers studies have highlighted crucial role macrophages cardiac repair following MI, timely targeting immune response via may represent a promising therapeutic avenue. Recently, technology such single-cell sequencing has provided us updated in-depth understanding Meanwhile, development biomaterials made it possible macrophage-targeted therapy. Thus, overall thorough current status macrophage-based therapy will assist study post-infarction remodeling. This review synthesizes spatiotemporal dynamics, function, mechanism signaling process discusses emerging bio-materials agents HF.

Language: Английский

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Causal relationship between immune cells and risk of myocardial infarction: evidence from a Mendelian randomization study

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 27, 2024

Background Atherosclerotic plaque rupture is a major cause of heart attack. Previous studies have shown that immune cells are involved in the development atherosclerosis, but different play roles. The aim this study was to investigate causal relationship between immunological traits and myocardial infarction (MI). Methods To assess association profiles with based on publicly available genome-wide studies, we used two-sample mendelian randomization (MR) approach inverse variance weighted (IVW) as main analytical method. Sensitivity analyses were heterogeneity horizontal pleiotropy. Results A MR analysis conducted using IVW primary At significance level 0.001, identified 47 immunophenotypes significant MI. Seven these present B cells, five cDC, four T at maturation stage, six monocytes, myeloid 12 TBNK eight Treg cells. performed confirm robustness results. Conclusions Our results provide strong evidence multiple effect risk infarction. This discovery provides new avenue for therapeutic treatments target drug development.

Language: Английский

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Novel 3-D macrophage spheroid model reveals reciprocal regulation of immunomechanical stress and mechano-immunological response

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 17, 2024

Purpose: In many diseases, an overabundance of macrophages contributes to adverse outcomes. While numerous studies have compared macrophage phenotype after mechanical stimulation or with varying local stiffness, it is unclear if and how themselves contribute forces in their microenvironment. Methods: Raw 264.7 murine were embedded a confining agarose gel, where they proliferated form spheroids over time. Gels synthesized at various concentrations tune the stiffness treated growth supplements promote polarization. The then analyzed by immunofluorescent staining qPCR for markers proliferation, mechanosensory channels, Finally, spheroid geometries used computationally model strain generated growth. Results: Macrophages generate growth-induced (i.e., solid stress) within gels, which can be maintained least 16 days culture. Increasing concentration restricts expansion, promotes discoid geometries, limits gel deformation, induces increase iNOS expression. LPS increases growth, though this effect reversed addition IFN-γ. Ki67 expression decreases increasing concentration, line measurements. Conclusions: alone both respond stress. Understanding generation stress responds different environmental conditions will help inform treatment strategies plethora diseases that involve accumulation.

Language: Английский

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Functional transformation of macrophage mitochondria in cardiovascular diseases

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Language: Английский

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Pathophysiology of Angiotensin II-Mediated Hypertension, Cardiac Hypertrophy, and Failure: A Perspective from Macrophages

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 2001 - 2001

Published: Dec. 4, 2024

Heart failure is a complex syndrome characterized by cardiac hypertrophy, fibrosis, and diastolic/systolic dysfunction. These changes share many pathological features with significant inflammatory responses in the myocardium. Among various regulatory systems that impact on these heterogeneous processes, angiotensin II (Ang II)-activated macrophages play pivotal role induction of subcellular defects adverse remodeling during progression heart failure. Ang stimulates via its AT1 receptor to release oxygen-free radicals, cytokines, chemokines, other mediators myocardium, upregulates expression integrin adhesion molecules both monocytes endothelial cells, leading monocyte-endothelial cell-cell interactions. The transendothelial migration monocyte-derived exerts biological effects proliferation fibroblasts, deposition extracellular matrix proteins, perivascular/interstitial development hypertension, hypertrophy Inhibition macrophage activation using antagonist or depletion from peripheral circulation has shown inhibitory II-induced vascular myocardial injury. purpose this review discuss current understanding maladaptive dysfunction, particularly focusing molecular signaling pathways involved macrophages-mediated In addition, challenges remained translating findings treatment patients are also addressed.

Language: Английский

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The Macrophage–Fibroblast Dipole in the Context of Cardiac Repair and Fibrosis

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1403 - 1403

Published: Nov. 4, 2024

Stromal and immune cells their interactions have gained the attention of cardiology researchers clinicians in recent years as contribution cardiac repair is increasingly recognized. The process heart a particularly critical constellation complex molecular cellular events that characteristically fail to ensure adequate recovery following injury, insult, or exposure stress conditions this regeneration-hostile organ. tremendous consequence pronounced inability maintain homeostatic states being translated numerous ways promoting progress into failure, deadly, irreversible condition requiring organ transplantation. Fibrosis fact response eventually dysfunction fibroblasts are major players process, overproducing collagens other extracellular matrix components when activated. On hand, macrophages may differentially affect depending on status subsets. opposite interaction also probable. We discuss here multifaceted aspects crosstalk cell dipole opportunities it offer for beneficial manipulation approaches will hopefully lead disease interventions.

Language: Английский

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The Role of Cardiac Macrophages in Inflammation and Fibrosis after Myocardial Ischemia-Reperfusion

Reviews in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 25(11)

Published: Nov. 21, 2024

According to current statistics, the mortality rate of cardiovascular diseases remains high, with coronary artery disease being primary cause death. Despite widespread adoption percutaneous intervention (PCI) in recent years, which has led a notable decrease myocardial infarction (MI), pathological cardiac remodeling and heart failure that follow still pose significant clinical challenges. Myocardial ischemia-reperfusion (MIR) injury represents complex pathophysiological process, involvement macrophages this consistently been subject focus. Following MIR, infiltrate, engulfing tissue debris necrotic cells, secreting pro-inflammatory factors. This initial response is crucial for clearing damaged tissue. Subsequently, (M1) transition an anti-inflammatory phenotype (M2), shift essential fibrosis remodeling. process dynamic, complex, continuous. To enhance understanding review elaborates on classification functions within heart, covering research signaling pathways involved through subsequent MIR fibrosis. The ultimate aim reduce injury, foster conducive environment recovery, improve outcomes MI patients.

Language: Английский

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Cardioprotective effects of glatiramer acetate after ischemic myocardial injury

Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(9), P. 1024 - 1025

Published: Aug. 26, 2024

Language: Английский

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