The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Open accessAbstract
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Oxidized low-density lipoprotein (LDsL), a cholesterol carrier, can also form crystals within lysosomes after internalization [74].”
From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [74]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Elevation of CEs and BMPs was also observed in LOAD patients’ EC, suggesting disease relevance.43”
From Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist (2024) · cites this paper as [44]
Experimental — accuracy not yet measuredIn the citing paper
“Oxidized low‐density lipoprotein and cholesterol crystals activate the inflammasome, thereby leading to the processing and secretion of the proinflammatory cytokines IL‐1β and IL‐18 and ultimately triggering vascular inflammation via upregulation of adhesion molecules.9, 10”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [10]
In the citing paper
“AS is decreased in several rodent models lacking NLRP3 or IL‐1 molecules, whereas in contrast, mice deficient in the IL‐1 receptor antagonist show increased AS.10”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [10]
In the citing paper
“These results clearly indicate that the NLRP3 inflammasome plays a key role in the pathogenesis of vascular inflammation, thereby contributing to AS development.”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [10]
In the citing paper
“Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inflammasome, a cytosolic receptor complex that plays a critical role in driving inflammatory immune responses.”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [20]
In the citing paper
“The NLRP3 inflammasome senses crystalline danger signals that can occur during autoinflammatory diseases, such as gout or atherosclerosis, and environmental diseases, such as silicosis or asbestosis (18, 20, 22).”
From Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages (2018) · cites this paper as [20]
In the citing paper
“inflammasome-dependent cytokine synthesis and release is a two-step process that is initiated after ligation of TLRs and other receptors capable of binding DAMPS and/or MAMPs leading to NLRP3 gene transcription, translation, and protein production (Duewell et al, 2010).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Duewell et al, 2010
In the citing paper
“Urate and cholesterol crystals, as well as sterile particulates, for example, can bypass the requirement for ATP and P2RX7 for IL-1β production55,59.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
In the citing paper
“For these sterile particulates to activate NLRP3, they must be internalized, as blockade of endocytosis by the actin-depolymerizing drug cytochalasin D inhibited NLRP3-dependent IL-1β production58,59.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
In the citing paper
“Low-density lipoprotein (LDL) receptor-deficient mice, which are prone to developing atherosclerotic lesions, had lower IL-1β levels, smaller atherosclerotic lesions and less neutrophilic infiltration than wild-type mice when lethally irradiated and infused with NLRP3-deficient bone marrow59.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
In the citing paper
“Lysosomal damage can occur during cellular injury and necrosis, and has also been associated with other sterile activators of NLRP3, such as cholesterol59 and silica crystals44.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
In the citing paper
“However, cathepsin b-deficient macrophages have no impairment in IL-1β production in response to certain NLRP3 agonists, including LPS plus ATP, or MSU crystals, despite the impairment in their response to silica44,56,59,67.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
In the citing paper
“Furthermore, there is only partial inhibition of the neutrophil infiltration and IL-1β production associated with sterile inflammation in response to cholesterol crystals44,56,59,67.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
In the citing paper
“evidence to support this are the observations that artificial lysosomal rupture alone can activate NLRP3 and that pharmacological inhibition or genetic depletion of cathepsin b results in inhibition of caspase 1 activation, although this inhibition was only partial44,56,59.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
High density lipoprotein as a protective factor against coronary heart disease
Gordon, T., Castelli, W. P., Hjortland, M. C., Kannel, W. B., & Dawber, T. R. (1977) · The American Journal of Medicine · doi:10.1016/0002-9343(77)90874-9 · Cited by 5,059
Stary, H. C., Chandler, A. B., Dinsmore, R. E., Fuster, V., Glagov, S. K., Insull, W., Rosenfeld, M. E., Schwartz, C. J., Wagner, W. D., & Wissler, R. W. (1995) · Circulation · doi:10.1161/01.cir.92.5.1355 · Cited by 3,506
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466
Bauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,087
Self-citationHornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Self-citationInnate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
Self-citationThe NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
Self-citationThe Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 401–500 of 1,023
NLRP3 inflammasome pathways in atherosclerosis
Baldrighi, M., Mallat, Z., & Li, X. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.10.027 · Cited by 204
Cathepsin B Is Required for NLRP3 Inflammasome Activation in Macrophages, Through NLRP3 Interaction
Chevriaux, A., Pilot, T., Dérangère, V., Simonin, H., Martine, P., Chalmin, F., Ghiringhelli, F., & Rébé, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00167 · Cited by 202
NOD-like receptors and the innate immune system: Coping with danger, damage and death
Kersse, K., Bertrand, M. J. M., Lamkanfi, M., & Vandenabeele, P. (2011) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2011.09.003 · Cited by 214
“In addition, several stimuli, mostly particulate ones, were shown to rely on lysosomal rupture for NLRP3 inflammasome assembly [102,126,127,131,186,191–194].”
BackgroundNLRP3 Inflammasome as a Novel Player in Myocardial Infarction
Takahashi, M. (2014) · International Heart Journal · doi:10.1536/ihj.13-388 · Cited by 200
The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging
Meyers, A. K., & Zhu, X. (2020) · Cells · doi:10.3390/cells9081808 · Cited by 207
“Atherogenic factors such as cholesterol crystals [87] and oxidized LDL [88] activate the NRLP3 inflammasome.”
Backgroundα-Synuclein Alters Toll-Like Receptor Expression
Béraud, D., Twomey, M. A., Bloom, B., Mittereder, A., Ton, V., Neitzke, K., Chasovskikh, S., Mhyre, T. R., & Maguire‐Zeiss, K. A. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00080 · Cited by 203
“…non-pathogen related forms of inflammation in which endogenous, disease-related signals, “danger/ damage-associated molecular patterns” (DAMPs), are recognized by microglia via PRRs and result in activation (Halle et al., 2008; Chen and Nunez, 2010; Duewell et al., 2010; Stewart et al., 2010).”
BackgroundDiverse Roles of Macrophages in Atherosclerosis: From Inflammatory Biology to Biomarker Discovery
Gui, T., Shimokado, A., Sun, Y., Akasaka, T., & Muragaki, Y. (2012) · Mediators of Inflammation · doi:10.1155/2012/693083 · Cited by 209
Adaptive immunity in atherogenesis: new insights and therapeutic approaches
Lichtman, A. H., Binder, C. J., Tsimikas, S., & Witztum, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci63108 · Cited by 201
Kalantari, P., DeOliveira, R. B., Chan, J., Corbett, Y., Rathinam, V. A. K., Stutz, A., Latz, E., Gazzinelli, R. T., Golenbock, D. T., & Fitzgerald, K. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.014 · Cited by 198
Self-citationMultiple roles of caspase-8 in cell death, inflammation, and innate immunity
Ørning, P., & Lien, E. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0420-305r · Cited by 206
Self-citationImazio, M., & Nidorf, M. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab221 · Cited by 209
The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation
Campden, R. I., & Zhang, Y. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.02.015 · Cited by 203
Innate sensors of pathogen and stress: Linking inflammation to obesity
Jin, C., & Flavell, R. A. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.06.022 · Cited by 197
Vajjhala, P. R., Mirams, R. E., & Hill, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.381228 · Cited by 205
Zeng, W., Wu, D., Sun, Y., Suo, Y., Yu, Q., Zeng, M., Gao, Q., Yu, B., Jiang, X., & Wang, Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-98437-3 · Cited by 196
Of inflammasomes and pathogens – sensing of microbes by the inflammasome
Bauernfeind, F. G., & Hornung, V. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201201771 · Cited by 198
Self-citationArida, A., Protogerou, A. D., Kitas, G. D., & Sfikakis, P. P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071890 · Cited by 199
“Several studies have implicated the activation of NLRP3 and subsequent IL-1β secretion in the pathogenesis of RA, as NLRP3 gene expression and caspase-1 and IL-1β levels were elevated in patients with active RA [158,159].”
BackgroundInfluentialTargeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases
Xu, C., Lu, Z.-D., Luo, Y., Liu, Y., Cao, Z., Shen, S., Li, H., Liu, J., Chen, K., Chen, Z., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06522-5 · Cited by 199
Zanoli, L., Briet, M. B., Empana, J. P., Cunha, P., Maki-Petaja, K. M., Protogerou, A. D., Tedgui, A., Touyz, R. M., Schiffrin, E. L., Spronck, B., et al. (2020) · Journal of Hypertension · doi:10.1097/hjh.0000000000002508 · Cited by 203
“Cholesterol crystals act as metabolic triggers of the NLRP3 inflammasome, which promotes the maturation of IL-1b and IL-18 [48].”
BackgroundInfluentialInduction of Inflammasome-dependent Pyroptosis by Carbon Black Nanoparticles
Reisetter, A. C., Stebounova, L. V., Baltrušaitis, J., Powers, L. S., Gupta, A. B., Grassian, V. H., & Monick, M. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.238519 · Cited by 197
Inflammation links excess fat to insulin resistance: the role of the interleukin‐1 family
Tack, C. J., Stienstra, R., Joosten, L. A. B., & Netea, M. G. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01145.x · Cited by 199
The Future of Cysteine Cathepsins in Disease Management
Kramer, L., Türk, V., & Turk, B. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.06.003 · Cited by 194
The arterial microenvironment: the where and why of atherosclerosis
Yurdagul, A., Finney, A. C., Woolard, M. D., & Orr, A. W. (2016) · Biochemical Journal · doi:10.1042/bj20150844 · Cited by 185
Krishnan, S. M., Dowling, J. K., Ling, Y. H., Diep, H., Chan, C. T., Ferens, D. M., Kett, M. M., Pinar, A. A., Samuel, C. S., Vinh, A., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13230 · Cited by 193
Self-citationLiver X Receptors in Atherosclerosis and Inflammation
Im, S., & Osborne, T. F. (2011) · Circulation Research · doi:10.1161/circresaha.110.226878 · Cited by 199
Usui, F., Shirasuna, K., Kimura, H. J., Tatsumi, K., Kawashima, A., Karasawa, T., Yoshimura, K., Aoki, H., Tsutsui, H., Noda, T., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303763 · Cited by 191
The NLRP3–inflammasome as a sensor of organelle dysfunction
Seoane, P. I., Lee, B., Hoyle, C., Yu, S., Lopez-Castejon, G., Lowe, M., & Brough, D. (2020) · Journal of Cell Biology · doi:10.1083/jcb.202006194 · Cited by 190
NLRP3 Inflammasomes Show High Expression in Aorta of Patients with Atherosclerosis
Zheng, F. Y., Xing, S., Gong, Z., & Xing, Q. (2013) · Heart Lung and Circulation · doi:10.1016/j.hlc.2013.01.012 · Cited by 191
“Recent studies suggested a strong link between inflammation and metabolic diseases, including obesity [3,4], type 2 diabetes [5], and atherosclerosis [6,7].”
BackgroundUpdated insights into the molecular networks for NLRP3 inflammasome activation
Paik, S., Kim, J. K., Shin, H. J., Park, E., Kim, I. S., & Jo, E. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01284-9 · Cited by 222
Mulay, S. R., Evan, A. P., & Anders, H. (2013) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gft248 · Cited by 190
Innate Immune Receptors: Key Regulators of Metabolic Disease Progression
Jin, C., Henao‐Mejia, J., & Flavell, R. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.011 · Cited by 195
Schrijvers, D. M., Meyer, G. R. Y. D., & Martinet, W. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.224899 · Cited by 189
β-amyloid, microglia, and the inflammasome in Alzheimer’s disease
Gold, M., & El Khoury, J. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0518-0 · Cited by 187
Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation
Abela, G. S. (2010) · Journal of clinical lipidology · doi:10.1016/j.jacl.2010.03.003 · Cited by 192
Self-citationHyperuricemia-induced inflammasome and kidney diseases
Isaka, Y., Takabatake, Y., Takahashi, A., Saitoh, T., & Yoshimori, T. (2015) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfv024 · Cited by 192
Cholesterol Crystals and Inflammation
Grebe, A., & Latz, E. (2013) · Current Rheumatology Reports · doi:10.1007/s11926-012-0313-z · Cited by 192
Self-citationEndothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation
Zhuang, T., Liu, J., Chen, X., Zhang, L., Pi, J., Sun, H., Li, L., Bauer, R. C., Wang, H., Yu, Z., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314402 · Cited by 188
Neutrophil Extracellular Traps and Cardiovascular Diseases: An Update
Bonaventura, A., Vecchié, A., Abbate, A., & Montecucco, F. (2020) · Cells · doi:10.3390/cells9010231 · Cited by 193
“Cholesterol crystals are recognized as important drivers in atherosclerosis [98], as supported by studies in mice with defective cholesterol efflux [99,100].”
BackgroundNLRP3 inflammasome as a key driver of vascular disease
Takahashi, M. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab010 · Cited by 193
Mirshafiee, V., Sun, B., Chang, C. H., Liao, Y., Jiang, W., Jiang, J., Liu, X., Wang, X., Xia, T., & Nel, A. E. (2018) · ACS Nano · doi:10.1021/acsnano.8b01086 · Cited by 189
Martin, S. J. (2016) · FEBS Journal · doi:10.1111/febs.13775 · Cited by 188
The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors
Zhan, X., Li, Q., Xu, G., Xiao, X., & Bai, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1109938 · Cited by 203
“Furthermore, it has been reported that cholesterol crystal, a hallmark of atherosclerotic lesions (80), activates NLRP3 inflammasome in a process involving lysosomal rupture, and reconstitution with NLRP3-, ASC-, or IL-1a/b–deficient bone marrow in low-density lipoprotein receptor (LDLR)–deficient mice shows reduced e…”
BackgroundTrem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis
Patterson, M. T., Firulyova, M. M., Xu, Y., Hillman, H., Bishop, C., Zhu, A., Hickok, G. H., Schrank, P. R., Ronayne, C. E., Caillot, Z., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00354-3 · Cited by 204
“1c, it may not be surprising if many of these cells undergo inflammasome-mediated pyroptosis 50,51 .”
BackgroundInflammasomes: far beyond inflammation
Henao‐Mejia, J., Elinav, E., Strowig, T., & Flavell, R. A. (2012) · Nature Immunology · doi:10.1038/ni.2257 · Cited by 188
Nuclear Factor E2-related Factor-2 (Nrf2) Is Required for NLRP3 and AIM2 Inflammasome Activation
Zhao, C., Gillette, D. D., Li, X., Zhang, Z., & Wen, H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.563114 · Cited by 190
Lipid droplet proteins and metabolic diseases
Xu, S., Zhang, X., & Liu, P. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.07.019 · Cited by 192
Symptomatic and asymptomatic carotid artery plaque
Mughal, M. M., Khan, M., DeMarco, J. K., Majid, A., Shamoun, F. E., & Abela, G. S. (2011) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.11.120 · Cited by 184
Self-citationTomalka, J. A., Ganesan, S., Azodi, E., Patel, K., Majmudar, P. R., Hall, B. A., Fitzgerald, K. A., & Hise, A. G. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002379 · Cited by 188
Self-citationUsui, F., Shirasuna, K., Kimura, H. J., Tatsumi, K., Kawashima, A., Karasawa, T., Hida, S., Sagara, J., Taniguchi, S., & Takahashi, M. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.058 · Cited by 183
Mishra, A., Zheng, J., Tang, X., & Goering, P. L. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw011 · Cited by 186
How Oxidized Low-Density Lipoprotein Activates Inflammatory Responses
Rhoads, J. P., & Major, A. S. (2018) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2018026483 · Cited by 184
Ultrasound In-Depth Characterization and Staging of Hidradenitis Suppurativa
Wortsman, X., Moreno, C., Soto, R., Arellano, J., Pezo, C., & Wortsman, J. (2013) · Dermatologic Surgery · doi:10.1111/dsu.12329 · Cited by 182
NLRP3 Suppresses NK Cell–Mediated Responses to Carcinogen-Induced Tumors and Metastases
Chow, M. T., Sceneay, J., Paget, C., Wong, C. S. F., Duret, H., Tschopp, J., Möller, A., & Smyth, M. J. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0509 · Cited by 189
Ogg1 -Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis
Tumurkhuu, G., Shimada, K., Dagvadorj, J., Crother, T. R., Zhang, W., Luthringer, D., Gottlieb, R. A., Chen, S., & Arditi, M. (2016) · Circulation Research · doi:10.1161/circresaha.116.308362 · Cited by 182
“mitochondrial (mt) function as the central hub for integrating these various signals.(5,8,9) We recently showed that during apoptosis/pyroptosis, mitochondrial DNA (mtDNA) damaged by oxidative stress activates the NLRP3 inflammasome, releasing active IL-1β.”
The Role of Inflammation in the Pathogenesis of Preeclampsia
Michalczyk, M., Celewicz, A., Celewicz, M., Woźniakowska-Gondek, P., & Rzepka, R. (2020) · Mediators of Inflammation · doi:10.1155/2020/3864941 · Cited by 205
“It is distinguished by its two major features: its activation can be triggered by a variety unrelated factors (including PAMPs, DAMPs, and alarmins) [95, 96], and it is highly expressed on the cells of innate immune system (macrophages, neutrophils, and dendritic cells) in many tissues [97, 98].”
BackgroundDekker, C., Mattes, H., Wright, M., Boettcher, A., Hinniger, A., Hughes, N., Kapps-Fouthier, S., Eder, J., Erbel, P. J. A., Stiefl, N., et al. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167309 · Cited by 183
Farrell, G. C., Haczeyni, F., & Chitturi, S. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-10-8684-7_3 · Cited by 178
Xanthine Oxidase Inhibition by Febuxostat Attenuates Experimental Atherosclerosis in Mice
Nomura, J., Busso, N., Ives, A., Matsui, C., Tsujimoto, S., Shirakura, T., Tamura, M., Kobayashi, T., So, A., & Yamanaka, Y. (2014) · Scientific Reports · doi:10.1038/srep04554 · Cited by 181
Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis
Yuan, Y., Li, P., & Ye, J. (2012) · Protein & Cell · doi:10.1007/s13238-012-2025-6 · Cited by 181
“Moreover, the cholesterol crystals in macrophages promote the maturation and secretion of interleukin-1β (IL-1β) and IL-18 (Duewell et al., 2010).”
Hu, Q., Zhang, T., Yi, L., Zhou, X., & Mi, M. (2017) · BioFactors · doi:10.1002/biof.1395 · Cited by 180
The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence
Youm, Y.-H., Kanneganti, T.-D., Vandanmagsar, B., Zhu, X., Ravussin, A., Adijiang, A., Owen, J. S., Thomas, M. J., Francis, J., Parks, J. S., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2011.11.005 · Cited by 172
Kahlenberg, J. M., Thacker, S. G., Berthier, C. C., Cohen, C. D., Kretzler, M., & Kaplan, M. J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101284 · Cited by 179
Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH
Ioannou, G. N., Subramanian, S., Chait, A., Haigh, W. G., Yeh, M. M., Farrell, G. C., Lee, S. P., & Savard, C. E. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m072454 · Cited by 180
Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease
Wang, Q., Wu, J., Zeng, Y., Chen, K., Wang, C., Yang, S., Sun, N., Chen, H., Duan, K., & Zeng, G. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.06.044 · Cited by 180
Silvis, M. J. M., Dengler, S. E. K. G., Odille, C. A., Mishra, M., van der Kaaij, N. P., Doevendans, P. A., Sluijter, J. P. G., de Kleijn, D. P. V., de Jager, S. C. A., Bosch, L., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.599511 · Cited by 194
Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes
Legrand-Poels, S., Esser, N., L’homme, L., Scheen, A., Paquot, N., & Piette, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.08.013 · Cited by 194
“evidence shows that the NLRP3 inflammasome plays a role in several metabolic diseases such as gout [113], Alzheimer’s disease [114] and atherosclerosis [115].”
BackgroundProgrammed Necrosis and Disease:We interrupt your regular programming to bring you necroinflammation
Kim, E. H., Wong, S., & Martinez, J. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0179-3 · Cited by 181
Abderrazak, A., Couchie, D., Mahmood, D. F. D., Elhage, R., Vindis, C., Laffargue, M., Mateo, V., Büchele, B., Ayala, M. R., Gaafary, M. E., et al. (2015) · Circulation · doi:10.1161/circulationaha.114.013730 · Cited by 177
Macrophages in the Aging Liver and Age-Related Liver Disease
Stahl, E. C., Haschak, M. J., Popovic, B., & Brown, B. N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02795 · Cited by 171
“Numerous DAMPs, which have been shown to promote inflammasome formation and activation, also have age-related increases in concentration, including cholesterol (111), amyloid-β (112, 113), hydroxyapatite crystals (114), purine catabolic end products such as uric acid (115), and ATP (116).”
BackgroundKushiyama, A., Nakatsu, Y., Matsunaga, Y., Yamamotoya, T., Mori, K., Ueda, K., Inoue, Y., Sakoda, H., Fujishiro, M., Ono, H., et al. (2016) · Mediators of Inflammation · doi:10.1155/2016/8603164 · Cited by 188
Clinician’s Guide to Reducing Inflammation to Reduce Atherothrombotic Risk
Ridker, P. M. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.06.082 · Cited by 186
“The NLRP3 inflammasome in turn is activated by several physiological processes including contact with crystalline structures, the most prominent of which for atherosclerosis is crystalline cholesterol (41).”
BackgroundPrevention of atherosclerosis from childhood
Raitakari, O. T., Pahkala, K., & Magnussen, C. G. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00647-9 · Cited by 197
The World Goes Bats: Living Longer and Tolerating Viruses
Gorbunova, V., Seluanov, A., & Kennedy, B. K. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.013 · Cited by 162
Elimination of the NLRP3-ASC Inflammasome Protects against Chronic Obesity-Induced Pancreatic Damage
Youm, Y., Adijiang, A., Vandanmagsar, B., Burk, D. H., Ravussin, A., & Dixit, V. D. (2011) · Endocrinology · doi:10.1210/en.2011-1326 · Cited by 187
Inflammasomes and host defenses against bacterial infections
Vladimer, G. I., Marty-Roix, R., Ghosh, S., Weng, D., & Lien, E. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2012.11.008 · Cited by 173
Self-citationThe Inflammasome in Atherosclerosis and Type 2 Diabetes
Masters, S. L., Latz, E., & O’Neill, L. A. J. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001902 · Cited by 169
Self-citationJacobsen, K., Lund, M. B., Shim, J., Gunnersen, S., Füchtbauer, E.-M., Kjolby, M., Carramolino, L., & Bentzon, J. F. (2017) · JCI Insight · doi:10.1172/jci.insight.95890 · Cited by 172
Expression of the NLRP3 Inflammasome in Carotid Atherosclerosis
Shi, X., Xie, W., Kong, W.-W., Chen, D., & Qu, P. (2015) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2015.03.024 · Cited by 180
Béraud, D., Hathaway, H. A., Trecki, J., Chasovskikh, S., Johnson, D. A., Johnson, J. A., Federoff, H. J., Shimoji, M., Mhyre, T. R., & Maguire‐Zeiss, K. A. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9401-0 · Cited by 179
Inflammation: a culprit for vascular calcification in atherosclerosis and diabetes
Bessueille, L., & Magne, D. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1876-4 · Cited by 182
Chistiakov, D. A., Bobryshev, Y. V., Nikiforov, N. G., Elizova, N. V., Sobenin, I. A., & Orekhov, A. N. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.03.055 · Cited by 184
RetractedLeng, W., Ouyang, X., Lei, X., Wu, M., Chen, L., Wu, Q., Deng, W., & Liang, Z. (2016) · Mediators of Inflammation · doi:10.1155/2016/6305735 · Cited by 174
Liver X Receptors: Regulators of Cholesterol Metabolism, Inflammation, Autoimmunity, and Cancer
Bilotta, M. T., Petillo, S., Santoni, A., & Cippitelli, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.584303 · Cited by 180
Impact of intracellular innate immune receptors on immunometabolism
Chou, W.-C., Rampanelli, E., Li, X., & Ting, J. P. ‐. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00780-y · Cited by 173
IL-1 family cytokines trigger sterile inflammatory disease
Lukens, J. R., Gross, J. M., & Kanneganti, T. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00315 · Cited by 178
“For example, LDLreceptor-deficient mice (genetically prone to atherosclerosis) that are reconstituted with bone marrow cells from mice that lack NLRP3, ASC, or IL-1β are remarkably resistant to plaque formation (Duewell et al., 2010).”
BackgroundTherapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk
Goldfine, A. B., & Shoelson, S. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88884 · Cited by 176
NLRP3: A Novel Mediator in Cardiovascular Disease
Zhou, W., Chen, C., Chen, Z., Liu, L., Jiang, J., Wu, Z., Zhao, M., & Chen, Y. (2018) · Journal of Immunology Research · doi:10.1155/2018/5702103 · Cited by 171
Botts, S. R., Fish, J. E., & Howe, K. L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.787541 · Cited by 181
“Promoting Inflammation Resolution to Mitigate Atherosclerosis The NLRP3 inflammasome is now recognized as a key player in the coordination of vascular inflammation and onset of atherogenesis (Duewell et al., 2010; Jin and Fu, 2019).”
BackgroundHsu, C. G., Chávez, C. L., Zhang, C., Sowden, M. P., Chen, Y., & Berk, B. C. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00966-5 · Cited by 174
“Recent data suggest that endogenous lipids or their oxidation products can activate or inhibit the assembly of inflammasomes [5, 14].”
BackgroundTreating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies
Cavalli, G., & Dinarello, C. A. (2015) · Rheumatology · doi:10.1093/rheumatology/kev269 · Cited by 178
Hu, Q., Zhang, X., Pan, Y., Li, Y., & Kong, L. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.03.005 · Cited by 174
“Uric acid and lipid are the danger signals to activate the NLRP3 inflammasome [4,10,42,43].”
BackgroundThe intersection of cell death and inflammasome activation
Vince, J. E., & Silke, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2205-2 · Cited by 180
Focal Arterial Inflammation Precedes Subsequent Calcification in the Same Location
Abdelbaky, A., Corsini, E. M., Figueroa, A. L., Fontanez, S., Subramanian, S. S., Ferencik, M., Brady, T. J., Hoffmann, U., & Tawakol, A. A. (2013) · Circulation Cardiovascular Imaging · doi:10.1161/circimaging.113.000382 · Cited by 176
Vascular Macrophages in Atherosclerosis
Xu, H., Jiang, J., Chen, W., Li, W., & Chen, Z. (2019) · Journal of Immunology Research · doi:10.1155/2019/4354786 · Cited by 176
“Crystalline cholesterol induces IL-1 family cytokines in macrophages by stimulating the caspase-1-activated nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome [68].”
BackgroundPCSK9 Biology and Its Role in Atherothrombosis
Barale, C., Melchionda, E., Morotti, A., & Russo, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115880 · Cited by 180
“The accumulation of cholesterol crystals, mainly due to the imbalance between esterified and free cholesterol, promotes the activation of the innate immune signaling complex nucleotide-binding and oligomerization domain (NOD)-like receptor pyrine domain-containing protein 3 (NLRP3) inflammasome [79], the key mediator…”
BackgroundNiyonzima, N., Rahman, J., Kunz, N., West, E. E., Freiwald, T., Desai, J. V., Merle, N. S., Gidon, A., Sporsheim, B., Lionakis, M. S., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abf2489 · Cited by 172
Self-citationThe role of NLRP3 inflammasome in 5-fluorouracil resistance of oral squamous cell carcinoma
Feng, X., Luo, Q., Zhang, H., Wang, H., Chen, W., Meng, G., & Chen, F. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0553-x · Cited by 171
Macrophage Recognition of Crystals and Nanoparticles
NAKAYAMA, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00103 · Cited by 173
Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis
He, X., Fan, X., Bai, B., Lu, N., Zhang, S., & Zhang, L. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105447 · Cited by 174
Zeller, M. V., Dias, D., Sebastião, A. M., & Valente, C. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210268 · Cited by 179
“crystals [68], cholesterol crystals [69], and aggre-”
Metadata
- Authors
- Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., Espevik, T., Lien, E., Fitzgerald, K. A., Rock, K. L., Moore, K. J., Wright, S. D., Hornung, V., & Latz, E.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Harvard University (US)
- Michigan State University (US)
- University of Michigan (US)
- Ludwig-Maximilians-Universität München (DE)
- Norwegian University of Science and Technology (NO)
- CSL (Australia) (AU)
- University of Bonn (DE)
- Corresponding author
- Latz, Eicke
- ORCID
- Venue
- Nature
- Published
- 2010-04-01
- Volume
- 464
- Issue
- 7293
- Pages
- 1357-1361
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2946640
- OpenAlex
- W1972483153
- Cited by
- 4,026
- References
- 31
- Citations by year
- 2026: 274 · 2025: 255 · 2024: 291 · 2023: 299 · 2022: 321 · 2021: 307 · 2020: 291 · 2019: 270 · 2018: 282 · 2017: 245 · 2016: 199 · 2015: 228 · 2014: 194 · 2013: 197 · 2012: 197
- FWCI
- 72.42
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-07-29)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL093262)
- National Institute of Allergy and Infectious Diseases (R01AI075318, R01AI083713)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- NLRP3 inflammasome, cholesterol crystals, atherogenesis, atherosclerosis, phagocytes, IL-1β, IL-1α, cathepsin B, cathepsin L, ASC, caspase-1, LDL receptor, apolipoprotein E deficiency, high-cholesterol diet
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Cathepsin B, Cholesterol, Crystallization, Cytoskeletal Proteins, Diet, Atherogenic, Female, Humans, Inflammation, Interleukin-1, Lysosomes, Mice, Inbred C57BL, Peritoneal Cavity, Phagocytes, Receptors, LDL, Time Factors, Bone Marrow Transplantation, Interleukin-18, Atherosclerosis, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins, Cathepsin L
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
