Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: March 3, 2022

Circulating apolipoprotein B-containing lipoproteins, notably the low-density enter inner layer of arterial wall, intima, where a fraction them is retained and modified by proteases, lipases, oxidizing agents enzymes. The lipoproteins various modification products, such as fatty acids, ceramides, lysophospholipids, oxidized lipids induce inflammatory reactions in macrophages covering endothelial cells, initiating an increased leukocyte diapedesis. Lipolysis also induces formation cholesterol crystals with strong proinflammatory properties. Modified aggregated crystals, isolated from human atherosclerotic lesions, all can activate thereby secretion cytokines, chemokines, extent lipoprotein retention, modification, aggregation have been shown to depend largely on differences composition circulating particles. These properties be pharmacological means, provide opportunities for clinical interventions regarding prevention treatment vascular diseases.

Language: Английский

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Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses

EMBO Molecular Medicine, Journal Year: 2023, Volume and Issue: 15(5)

Published: March 10, 2023

Abstract Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin‐like kinase 1 (DCLK1), microtubule‐associated protein kinase, involved in neurogenesis human cancers. However, the role of DCLK1 atherosclerosis remains undefined. In this study, we identified upregulated macrophages atherosclerotic lesions ApoE −/− mice fed an HFD determined that macrophage‐specific deletion attenuates by reducing inflammation mice. Mechanistically, RNA sequencing analysis indicated mediates oxLDL‐induced via NF‐κB signaling pathway primary macrophages. Coimmunoprecipitation followed LC–MS/MS IKKβ as binding DCLK1. We confirmed directly interacts phosphorylates at S177/181, thereby facilitating subsequent activation gene expression Finally, pharmacological inhibitor prevents progression both vitro vivo. Our findings demonstrated macrophage promotes to activating IKKβ/NF‐κB. This study reports new regulator potential therapeutic target for atherosclerosis.

Language: Английский

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Protopine ameliorates OVA-induced asthma through modulatingTLR4/MyD88/NF-κB pathway and NLRP3 inflammasome-mediated pyroptosis

Phytomedicine, Journal Year: 2024, Volume and Issue: 126, P. 155410 - 155410

Published: Feb. 3, 2024

Chronic airway inflammation and hyperresponsiveness are characteristics of asthma. The isoquinoline alkaloid protopine (PRO) has been shown to exert anti-inflammatory effects, but its mechanism action in asthma is not known. Investigate the protective properties PRO upon elucidate mechanism. effects treatment were assessed by histology, biochemical analysis, real-time reverse transcription-quantitative polymerase chain reaction. Then, we integrated molecular docking, western blotting, cellular experiments, immunohistochemistry, immunofluorescence flow cytometry, metabolomics analysis reveal In vivo, therapy reduced number inflammatory cells (eosinophils, leukocytes, monocytes) bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations lung tissues, inhibited secretion lgG histamine. Molecular docking showed that could dock with proteins TLR4, MyD88, TRAF6, TAK1, IKKα, TNF-α. Western blotting displayed TLR4/NF-κB signaling pathway. regulated expression pyroptosis-related NLR family pyrin domain containing 3 (NLRP3) inflammasome, gasdermin D, caspase-1, drove caspase-1 inactivation affect responses inhibiting NLRP3 inflammasome. 24 h after PRO, cell activity, as well levels reactive oxygen species (ROS) interleukin (IL)-1β IL-18, decreased significantly. Immunofluorescence staining TLR4 MyD88 vitro. nuclear translocation NF-κB p65. Twenty-one potential biomarkers serum identified using they predominantly controlled metabolism phenylalanine, tryptophan, glucose, sphingolipids. OVA-induced underlying was associated TLR4/MyD88/NF-κB pathway inflammasome-mediated pyroptosis.

Language: Английский

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Challenges and advances in the management of inflammation in atherosclerosis

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Atherosclerosis, traditionally considered a lipid-related disease, is now understood as chronic inflammatory condition with significant global health implications. This review aims to delve into the complex interactions among immune cells, cytokines, and cascade in atherosclerosis, shedding light on how these elements influence both initiation progression of disease. draws recent clinical research elucidate roles key macrophages, T endothelial clonal hematopoiesis atherosclerosis development. It focuses cells process contribute disease progression, particularly through inflammation-driven processes that lead plaque formation stabilization. Macrophages ingest oxidized low-density lipoprotein (oxLDL), which partially converts high-density (HDL) or accumulates lipid droplets, forming foam crucial for stability. Additionally, macrophages exhibit diverse phenotypes within plaques, pro-inflammatory types predominating others specializing debris clearance at rupture sites. The involvement CD4+ CD8+ promotes macrophage states, suppresses vascular smooth muscle cell proliferation, enhances instability. nuanced related atherosclerotic microenvironment are explored, revealing insights cellular molecular pathways fuel inflammation. also addresses advancements imaging biomarker technology enhance our understanding progression. Moreover, it points out limitations current treatment highlights potential emerging anti-inflammatory strategies, including trials agents such p38MAPK, tumor necrosis factor α (TNF-α), IL-1β, their preliminary outcomes, promising effects canakinumab, colchicine, IL-6R antagonists. explores cutting-edge interventions, efficacy preventing alleviating role nanotechnology delivering drugs more effectively safely.

Language: Английский

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Haematometabolism rewiring in atherosclerotic cardiovascular disease

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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