Spatio-temporal dynamics of the fibrotic niche in cardiac repair DOI Creative Commons
Andy Chan, Joachim Greiner,

Tomás A. Brennan

et al.

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

Published: Nov. 11, 2024

Summary The heart is one of the least regenerative organs in humans, and ischemic disease leading cause death worldwide. Understanding cellular molecular processes that occur during cardiac wound healing an essential prerequisite to reducing health burden improve function after myocardial tissue damage. By integrating single-cell RNA-sequencing with imaging-based spatial transcriptomics, we reconstructed spatio-temporal dynamics fibrotic niche ventricular injury adult mice. Our analysis reveals dynamic regulation local cell communication niches over time. We identified interactions regulate repair, including fibroblast proliferation silencing by Trem2 high macrophages prevents excessive fibrosis. Moreover, discovered a rare population dedifferentiating cardiomyocytes early post-lesion stages, which was sustained signals from myeloid lymphoid cells. Culturing non-regenerative mouse or human these factors reactivated progenitor gene expression cycle activity. In summary, this type atlas provides valuable insights into heterocellular control repair. Highlights scRNA-seq situ sequencing reveal repair Local coordinate overall response Fibroblast suppresses fibrosis Cardiomyocyte plasticity promoted cells

Language: Английский

Inflammation‐Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment DOI
Danrong Hu, Ran Li, Yicong Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: April 6, 2024

Abstract Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction progression. Herein, mannan‐based nanomedicine, Que@MOF/Man, developed to target infarcted heart deliver antioxidative anti‐inflammatory agent quercetin (Que), thereby facilitating beneficial myocardial microenvironment for repair. The presence of mannan on nanoparticle surface enables selective internalization macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in reduce promote their differentiation into reparative phenotype, reconciling response enhancing cardiomyocyte survival through intercellular communication. Owing recruitment inflamed myocardium post‐MI, vivo, administration rats revealed specific distribution injured compared free Que. Furthermore, exhibited favorable results resolving inflammation protecting cardiomyocytes, preventing further remodeling improving function rats. These findings collectively validate rational design an inflammation‐targeted delivery strategy mitigate modulate heart, presenting therapeutic avenue treatment.

Language: Английский

Citations

17
Immunomodulation in non-alcoholic fatty liver disease: exploring mechanisms and applications DOI Creative Commons
Ziwei Guo,

Qinjuan Wu,

Pengfei Xie

et al.

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

Published: Jan. 30, 2024

Non-alcoholic fatty liver disease (NAFLD) exhibits increased lipid enrichment in hepatocytes. The spectrum of this includes stages such as nonalcoholic simple (NAFL), steatohepatitis (NASH), and fibrosis. Changes lifestyle behaviors have been a major factor contributing to the cases NAFLD patients globally. Therefore, it is imperative explore pathogenesis NAFLD, identify therapeutic targets, develop new strategies improve clinical management disease. Immunoregulation strategy through which organism recognizes eliminates antigenic foreign bodies maintain physiological homeostasis. In process, multiple factors, including immune cells, signaling molecules, cytokines, play role governing evolution NAFLD. This review seeks encapsulate advancements research regarding regulation spanning from underlying mechanisms practical applications.

Language: Английский

Citations

8
Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve DOI Creative Commons
Yuanyuan Li,

Ruoyao Xu,

Muyan Chen

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 13, 2025

Language: Английский

Citations

1
Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction DOI Creative Commons

Jing J. Zhang,

Rodrigue Rizk, Xiaoping Li

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Interleukin-10 (IL-10) is a potent immunomodulatory cytokine widely explored as therapeutic agent for diseases, including myocardial infarction (MI). High-dose IL-10 treatment may not achieve expected outcomes, raising the question of whether has dose-dependency, or even uncharted side-effects from overdosing. We hypothesized that dose-dependent effects on macrophage (Mφ) phenotypic transition and cardiac remodeling after MI. Using RAW264.7 monocyte models, we examined administering differential doses exogenous (0-1,000 ng/mL) perturbs classic M1 (pro-inflammatory) M2 (anti-inflammatory) phenotypes polarized Mφ alters prospective polarization. then investigated impact single intramyocardial administration function, structure, inflammation post-MI, using mouse MI model. Compared with 0-ng/mL control, 250-ng/mL had strongest overall in decreasing increasing while ≥500-ng/mL dampened polarization augmented native secretion more effectively than low vitro. Echocardiography revealed 250-ng group consistently higher contractile function lower left ventricular (LV) dilatation saline control over 6 weeks ≥1,000-ng groups exhibited transient LV ejection fraction at 5 days post-MI vivo. Moreover, different differentially modulated gene expression, phagocytic cell infiltration infarct, fibrosis, revascularization some, but all, exerting beneficial effects. Our study suggested an effective dose range phenotypes, trigger cardioprotective unwanted manner.

Language: Английский

Citations

1
Annexin A1-Loaded Alginate Hydrogel Promotes Cardiac Repair via Modulation of Macrophage Phenotypes after Myocardial Infarction DOI
Lingling Zhang, Lianbo Shao, Jingjing Li

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(5), P. 3232 - 3241

Published: April 1, 2024

Myocardial infarction (MI) is associated with inflammatory reaction, which a pivotal component in MI pathogenesis. Moreover, excessive inflammation post-MI can lead to cardiac dysfunction and adverse remodeling, emphasizing the critical need for an effective inflammation-regulating treatment repair. Macrophage polarization crucial process, indicating its potential as adjunct therapy MI. In this study, we developed injectable alginate hydrogel loaded annexin A1 (AnxA1, endogenous anti-inflammatory pro-resolving mediator) treatment. vitro results showed that composite had good biocompatibility consistently released AnxA1 several days. Additionally, led reduced number of pro-inflammatory macrophages increased proportion pro-healing via adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target rapamycin (mTOR) axis. Furthermore, intramyocardial injection into mouse model effectively modulated macrophage transition phenotypes. This mitigated early responses fibrosis, promoted angiogenesis, improved function. Therefore, our study findings suggest combining biomaterials proteins promising approach limiting preventing damage, preserving function infarcted hearts.

Language: Английский

Citations

5
Advances in macrophage metabolic reprogramming in myocardial ischemia-reperfusion DOI

Fan Ao-Di,

Lin Han-Qing,

Wang Xi-Zheng

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 123, P. 111370 - 111370

Published: Aug. 30, 2024

Language: Английский

Citations

4
GDF11 improves cardiac repair after myocardial infarction by reducing Macrophage infiltration and attenuating their inflammatory Properties DOI
Shushi Huang, WU Yu-ling, Ming‐Yao Chen

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113994 - 113994

Published: Jan. 7, 2025

Language: Английский

Citations

0
The Diagnostic Value of Bile Acids and Amino Acids in Differentiating Acute Coronary Syndromes DOI Creative Commons
Qian Yu, Furong Zhao, Shuang Wang

et al.

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 179 - 189

Published: Jan. 1, 2025

Acute coronary syndrome (ACS), comprising unstable angina and acute myocardial infarction, is the most dangerous fatal form of heart disease. This study evaluates serum bile acids (BAs) amino (AAs) as potential predictors AMI in UA patients. A total 72 Non-Coronary Artery Disease (NCAD) patients, 157 79 patients were analyzed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) measured 15 19 acids. The data was split into training validation sets (7:3). Univariate multivariate analyses performed. Diagnostic value clinical benefits assessed using receiver operating characteristic (ROC) curves, decision curve analysis, metrics such area under (AUC), integrated discrimination improvement (IDI), net reclassification (NRI). Orthogonal partial least squares discriminant analysis (OPLS-DA) BAs AAs effectively differentiated NCAD, UA, groups. differences BA AA profiles between primarily driven by four metabolites: deoxycholic acid (DCA), histidine (His), lysine (Lys), phenylalanine (Phe). Together, they had an AUC 0.830 (0.768 cohort) for predicting After adjusting multiple confounding factors, DCA, His, Lys, Phe independent distinguishing from AMI. results AUC, IDI, NRI showed that adding these biomarkers to a model with variables significantly improved predictive value, which confirmed cohort. These findings highlight association AMI, suggesting their role pathogenesis.

Language: Английский

Citations

0
Shuxuening injection improves myocardial injury after myocardial infarction by regulating macrophage polarization via the TLR4/NF-κB and PI3K/Akt signaling pathways DOI
Xiaoshuai Zhang, Liuqing Yang,

Kai‐Rui Feng

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 138, P. 156418 - 156418

Published: Jan. 23, 2025

Language: Английский

Citations

0
SPECT Imaging of Cardiac Inflammation by Targeting IL4 Receptor-α on Macrophages DOI

Danzha Zheng,

Mengyan Hu, Wenwen Wang

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

The inflammation response is a prominent sign of myocardial infarction (MI), mediating the process cardiac fibrosis and ventricular remodeling. Inflammation visualization holds new promise for guiding anti-inflammatory therapy. Interleukin-4 receptor α (IL4Rα) interacts with IL4, closely related to macrophage polarization. This study aimed evaluate feasibility technetium-99m (99mTc) labeled IL4Rα antibody probe ([99mTc]Tc-HYNIC-CM310) targeting postinfarction SPECT imaging. [99mTc]Tc-HYNIC-CM310 was prepared by radiolabeling an IL4Rα-specific monoclonal (CM310) 99mTc. Images were acquired at 0.5, 6, 12, 24, 36 h postinjection on next day after MI sham model preparation, biodistribution performed h. mean percentage injected dose per gram (%ID/g) various tissues obtained drawing regions interest. [18F]FDG metabolism imaging comparison verification. Immunofluorescence costaining flow cytometry conducted validate coexpression macrophages. yield approximately 88.31% ± 1.70%, radiochemical purity 93.70% 0.38%. accumulation in infarcted myocardium increased starting 12 postinjection. tracer uptake significantly higher than same site sham-operated rats (P < 0.05). region consistent metabolic defect inflammatory seen PET. staining confirmed colocalization IL4Rα+ cells markers myocardium. We successfully validated precise macrophages, offering opportunity treatment inflammation.

Language: Английский

Citations

0