Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis

Xiao, He; Fan, Xuehui; Bai, Bing; Lu, Nanjuan; Zhang, Shuang; Zhang, Liming

doi:10.1016/j.phrs.2021.105447

Cited by 111 publications

(83 citation statements)

References 191 publications

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“… 284 , 285 , 286 Thus, on the one hand, fatty acids, HG levels, and other metabolic signals could activate inflammasomes and pyroptosis, producing various inflammatory factors. 192 , 197 , 199 , 287 On the other hand, the metabolism statue also regulates the battle between immune cells and tumor cells 288 (Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, obesity and other diseases caused by metabolism dysregulation are accompanied by inflammation to different degrees, which may induce a tendency toward tumor development if the inflammation exists for a long time 284–286 . Thus, on the one hand, fatty acids, HG levels, and other metabolic signals could activate inflammasomes and pyroptosis, producing various inflammatory factors 192,197,199,287 . On the other hand, the metabolism statue also regulates the battle between immune cells and tumor cells 288 (Figure 5).…”

Section: Discussionmentioning

confidence: 99%

“…[284][285][286] Thus, on the one hand, fatty acids, HG levels, and other metabolic signals could activate inflammasomes and pyroptosis, producing various inflammatory factors. 192,197,199,287 On the other hand, the metabolism statue also regulates the battle between immune cells and tumor cells 288 (Figure 5). The success of immunotherapy is largely dependent on the high activity of intratumoral CD8 + T cells, and the therapeutic effect has been shown in some solid tumors such as melanoma and lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Pyroptosis is activated by various pathological conditions, which are known risk factors of atherosclerosis, including oxidative stress, hyperglycemia, dyslipidemia, and inflammation. 192 , 193 , 213 It is the first time that pyroptosis in vascular ECs has been reported to correlate with atherosclerotic progression, which can be partly attributed to ox‐LDL. 214 It has been found that ox‐LDL could induce pyroptosis via the ROS‐dependent pathway in ECs.…”

Section: The Relationship Between Pyroptosis and Metabolismmentioning

confidence: 99%

“…Pyroptosis is accompanied by inflammasome activation, GSDM and caspase cleavage, and cytokine releases, leading to inflammatory death in cells and expending inflammation in multi-tissues; all of these processes have impacts on a variety of metabolic disorders in different organs, including the liver, cardiovascular system, allergic and autoimmune diseases, diabetes, obesity, and others. In the case of the most studied NLRP3 inflammasome, which is a critical sensor of nutrient overload, this can be activated by various metabolic danger signals, such as uric acid crystals in gout, [189][190][191] cholesterol crystals and oxidized low-density lipoprotein (ox-LDL) in atherogenesis, [192][193][194][195] and glucose, fatty acids and islet amyloid polypeptide in T2D. [196][197][198][199] In response to infective pathogens and dangerous signaling molecules, profound metabolic fluctuation normally appears in immune cells.…”

Section: The Relationship Between Pyroptosis and Metabolismmentioning

confidence: 99%

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Pyroptosis, metabolism, and tumor immune microenvironment

Gao

et al. 2021

Clinical & Translational Med

178

121

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In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: The Relationship Between Pyroptosis and Metabolismmentioning

confidence: 99%

Section: The Relationship Between Pyroptosis and Metabolismmentioning

confidence: 99%

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Pyroptosis, metabolism, and tumor immune microenvironment

Gao

et al. 2021

Clinical & Translational Med

178

121

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Natural Cell Patches: Melanin Nanoparticles for MR Imaging‐Guided Antiatherosclerosis Therapy via Attenuating Macrophage Pyroptosis

Sheng

et al. 2023

Adv Funct Materials

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Pyroptosis, characterized by inflammasome activation, membrane Gasdermin D (GSDMD)-pore formulation, and the rapid release of inflammatory cytokines, can induce plaque instability and atherosclerosis progression. Nevertheless, insights into the precise antiatherosclerosis therapies targeting pyroptosis remain limited. Here, a novel biomedical application of natural polyphenol melanin as a theranostic antipyroptosis defense nanoplatform for atherosclerosis is reported. Ultrasmall melanin nanoparticles are easily fabricated and functionalized with cyclo-Arg-Gly-Asp-d-Tyr-Lys conjugated polyethylene glycol to yield cRGD-PEG-MNPs (RpMPs) to target plaque neovascularization, which is confirmed by fluorescence imaging. Importantly, RpMPs act like cell patches to suppress pyroptosis in lipopolysaccharidestimulated macrophages by scavenging reactive oxygen species, downregulating the expression levels of pyroptosis-related proteins (NLRP3, Caspase 1, and GSDMD) and reducing the leakage of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α). In vivo studies further reveal that RpMPs can ameliorate the development and improve the stability of atherosclerotic plaques via attenuating NLRP3-stimulated pyroptosis and inducing an anti-inflammatory phenotype in the aorta of ApoE −/− mice. Moreover, chelator-free Gd 3+ -RpMPs exhibit persistent T 1 -weighted contrast-enhanced efficiency and plaque resident on a 9.4 T Micro magnetic resonance scanner in murine atherosclerosis model. Overall, this study suggests the potential for using melanin to develop natural multifunctional nanoplatforms for molecular theranostic in atherosclerosis and other pyroptosis-related diseases.

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Engineering Nanoplatforms for Theranostics of Atherosclerotic Plaques

Liu,

Jiang,

Yang

et al. 2024

Adv Healthcare Materials

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Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post‐interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal‐to‐noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, we comprehensively summarize various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis. Additionally, we propose several therapeutic strategies to enhance the efficacy of treating atherosclerotic plaques. Finally, we discuss existing challenges and promising prospects for accelerating clinical translation of nanoplatform‐based molecular imaging and therapy for atherosclerotic plaques. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.This article is protected by copyright. All rights reserved

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Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis

Cited by 111 publications

References 191 publications

Pyroptosis, metabolism, and tumor immune microenvironment

Pyroptosis, metabolism, and tumor immune microenvironment

Natural Cell Patches: Melanin Nanoparticles for MR Imaging‐Guided Antiatherosclerosis Therapy via Attenuating Macrophage Pyroptosis

Engineering Nanoplatforms for Theranostics of Atherosclerotic Plaques

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