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
Cited by
Sorted by citations
Items 601–700 of 1,023
Moderate Hypoxia Potentiates Interleukin-1β Production in Activated Human Macrophages
Folco, E. J. E., Sukhova, G. K., Quillard, T., & Libby, P. (2014) · Circulation Research · doi:10.1161/circresaha.115.304437 · Cited by 148
Inflammation and cardiovascular diseases: lessons from seminal clinical trials
Liberale, L., Montecucco, F., Schwarz, L., Lüscher, T. F., & Camici, G. G. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa211 · Cited by 147
Jin, Y. H., Liu, Y., Xu, L., Xu, J., Xiong, Y., Peng, Y., Ding, K., Zheng, S., Yang, N., Zhang, Z., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04966-8 · Cited by 151
“In short, LDL receptor (Ldlr)–deficient (Ldlr) mice transplanted with bone marrow lacking Nlrp3, Asc, or IL-1β were athero-protective [9].”
LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis
Ding, Z., Liu, S., Wang, X., Dai, Y., Khaidakov, M., Deng, X., Fan, Y., Xiang, D., & Mehta, J. L. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu114 · Cited by 145
“Duewell et al.(18) first suggested that NLRP3 inflammasomes are required for atherogenesis.”
BackgroundVitamin B6 Prevents IL-1β Protein Production by Inhibiting NLRP3 Inflammasome Activation
Zhang, P., Tsuchiya, K., Kinoshita, T., Kushiyama, H., Suidasari, S., Hatakeyama, M., Imura, H., Katô, N., & Suda, T. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.743815 · Cited by 146
Wang, R., Wang, Y., Mu, N., Lou, X., Li, W., Chen, Y., Dong, F., & Tan, H. (2017) · Laboratory Investigation · doi:10.1038/labinvest.2017.30 · Cited by 144
miR-21 promotes NLRP3 inflammasome activation to mediate pyroptosis and endotoxic shock
Xue, Z., Xi, Q., Liu, H., Guo, X., Zhang, J., Zhang, Z., Li, Y., Yang, G., Zhou, D., Yang, H., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1713-z · Cited by 147
Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
Xu, G., Fu, S., Zhan, X., Wang, Z., Zhang, P., Shi, W., Qin, N., Chen, Y., Wang, C., Niu, M., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.134601 · Cited by 143
Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants
Olive, C. (2012) · Expert Review of Vaccines · doi:10.1586/erv.11.189 · Cited by 152
IL-1 in osteoarthritis: time for a critical review of the literature
Vincent, T. L. (2019) · F1000Research · doi:10.12688/f1000research.18831.1 · Cited by 146
“Although the presence of crystals in the joint does not necessarily lead to a clinical crystal arthritis, all crystals (including urate, pyrophosphate and cholesterol) are potential activators of the inflammasome pathway, resulting in caspase 1–dependent processing of intracellular pro–IL-1 75–77 .”
BackgroundComparison of non-crystalline silica nanoparticles in IL-1β release from macrophages
Sandberg, W. J., Låg, M., Holme, J. A., Friede, B., Gualtieri, M., Kruszewski, M. K., Schwarze, P. E., Skuland, T., & Refsnes, M. (2012) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-9-32 · Cited by 145
Phospholipase A2 enzymes and the risk of atherosclerosis
Rosenson, R. S., & Hurt‐Camejo, E. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs148 · Cited by 142
Atherosclerosis and Cancer; A Resemblance with Far-reaching Implications
Tapia-Vieyra, J. V., Delgado‐Coello, B., & Mas‐Oliva, J. (2017) · Archives of Medical Research · doi:10.1016/j.arcmed.2017.03.005 · Cited by 141
CAPS — pathogenesis, presentation and treatment of an autoinflammatory disease
Kuemmerle-Deschner, J. B. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0491-7 · Cited by 144
“In addition, activation may be achieved by reactive oxygen species (ROS), proteases released into the cytosol by lysosomal damage caused by amyloid-β, silica, cathepsin B or cholesterol crystals, or potassium efflux from the cell [21–24].”
BackgroundInhibiting the Inflammasome: A Chemical Perspective
Baldwin, A. G., Brough, D., & Freeman, S. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01091 · Cited by 142
Oxidative Stress in Oral Diseases: Understanding Its Relation with Other Systemic Diseases
Kumar, J., Teoh, S. L., Das, S., & Mahakknaukrauh, P. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00693 · Cited by 150
“NLRP3 inflammasome was reported to be activated by a host of molecules such as excess ROS, glucose, ATP, ceramides, sphingosine, crystals of cholesterol, uric acid, and oxidized LDL (Duewell et al., 2010; Jiang et al., 2012; Luheshi et al., 2012; Bandyopadhyay et al., 2013; Fukumoto et al., 2013).”
BackgroundWang, M., Zhao, J., Zhang, N., & Chen, J. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.07.025 · Cited by 141
Raman Imaging of Small Biomolecules
Shen, Y., Hu, F., & Min, W. (2019) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-052118-115500 · Cited by 138
Mechanisms of NLRP3 priming in inflammaging and age related diseases
Gritsenko, A., Green, J., Brough, D., & López‐Castejón, G. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.08.003 · Cited by 146
“Cholesterol crystals that appear in early atherosclerotic lesions can activate the NLRP3 inflammasome, causing caspase-1 cleavage and mIL-1 β release in a process associated with lysosomal rupture [102].”
BackgroundRRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor
Chen, Y., He, H., Lin, B., Chen, Y., Deng, X., Jiang, W., & Zhou, R. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00683-y · Cited by 142
Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses
Kiyotake, R., Oh‐hora, M., Ishikawa, E., Miyamoto, T., Ishibashi, T., & Yamasaki, S. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.645234 · Cited by 139
Katsnelson, M. A., Lozada‐Soto, K. M., Russo, H. M., Miller, B. A., & Dubyak, G. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00298.2015 · Cited by 141
Catapano, A. L., Pirillo, A., & Norata, G. D. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13805 · Cited by 138
Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases
Fenini, G., Contassot, E., & French, L. E. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00278 · Cited by 147
Hyperlipidemia-induced cholesterol crystal production by endothelial cells promotes atherogenesis
Baumer, Y., McCurdy, S., Weatherby, T. M., Mehta, N. N., Halbherr, S., Halbherr, P., Yamazaki, N., & Boisvert, W. A. (2017) · Nature Communications · doi:10.1038/s41467-017-01186-z · Cited by 138
Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production
Viaud, M., Ivanov, S., Vujić, N., Duta-Mare, M., Aira, L. E., Barouillet, T., Garcia, E., Orange, F., Dugail, I., Hainault, I., et al. (2018) · Circulation Research · doi:10.1161/circresaha.117.312333 · Cited by 148
Inflammasomes, neutrophil extracellular traps, and cholesterol
Tall, A. R., & Westerterp, M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.s091280 · Cited by 141
“(3) (see 4, 6, 24, 25), our own (7) and other studies (5) found no impact of deletion of the key inflammasome components, Nlrp3 or Caspase-1/11, on the area or morphology of either early or advanced lesions in WTD-fed Ldlr mice.”
BackgroundInflammasomes: Their Role in Normal and Complicated Pregnancies
Gomez‐Lopez, N., Motomura, K., Miller, D., Garcia‐Flores, V., Galaz, J., & Romero, R. J. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900901 · Cited by 136
Specific NLRP3 Inhibition Protects Against Diabetes-Associated Atherosclerosis
Sharma, A., Choi, J. S. Y., Stefanovic, N., Al‐Sharea, A., Simpson, D. S., Mukhamedova, N., Jandeleit-Dahm, K. A. M., Murphy, A. J., Sviridov, D., Vince, J. E., et al. (2020) · Diabetes · doi:10.2337/db20-0357 · Cited by 140
Cardiac metabolism in HFpEF: from fuel to signalling
Capone, F., Sotomayor-Flores, C., Bode, D., Wang, R., Rodolico, D., Strocchi, S., & Schiattarella, G. G. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac166 · Cited by 145
Cryopyrin-Associated Periodic Syndrome: An Update on Diagnosis and Treatment Response
Yu, J. R., & Leslie, K. S. (2010) · Current Allergy and Asthma Reports · doi:10.1007/s11882-010-0160-9 · Cited by 141
Context-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation
Miller, Y. I., & Shyy, J. Y.-J. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.11.002 · Cited by 141
Mantsounga, C., Lee, C. F., Neverson, J., Sharma, S., Healy, A. L., Berus, J. M., Parry, C., Ceneri, N. M., López‐Giráldez, F., Chun, H. J., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110309 · Cited by 143
“Cholesterol crystal inflammasome assay— Cholesterol crystals were generated as previously described (Duewell et al., 2010).”
Bauernfeind, F., Niepmann, S., Knolle, P. A., & Hornung, V. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501336 · Cited by 137
Self-citationCaspase-1 Deficiency Decreases Atherosclerosis in Apolipoprotein E-Null Mice
Gage, J., Hasu, M., Thabet, M., & Whitman, S. C. (2012) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2011.10.013 · Cited by 136
Schlesinger, N., Meulemeester, M. D., Pikhlak, A., Yücel, E., Richard, D., Murphy, V., Arulmani, U., Sallstig, P., & So, A. K.-L. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3297 · Cited by 138
Jiang, C., Jiang, L., Li, Q., Liu, X., Zhang, T., Dong, L., Liu, T., Liu, L., Hu, G.-L., Sun, X., et al. (2018) · Toxicology · doi:10.1016/j.tox.2018.09.002 · Cited by 137
The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals
Pang, C. E., Messinger, J. D., Zanzottera, E. C., Freund, K. B., & Curcio, C. A. (2015) · Ophthalmology · doi:10.1016/j.ophtha.2015.07.008 · Cited by 135
Fu, Y., Wang, Y., Du, L., Xu, C., Cao, J., Fan, T.-Q., Liu, J., Xu, S., Fan, S., Liu, Q., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140714105 · Cited by 136
Emerging roles for cholesterol and lipoproteins in lung disease
Gowdy, K. M., & Fessler, M. B. (2012) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2012.06.002 · Cited by 137
Disease-associated amyloid and misfolded protein aggregates activate the inflammasome
Masters, S. L., & O'Neill, L. A. J. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.01.005 · Cited by 134
Monocyte Recruitment, Specification, and Function in Atherosclerosis
Kim, K.-W., Ivanov, S., & Williams, J. W. (2020) · Cells · doi:10.3390/cells10010015 · Cited by 139
Challenges and advances in the management of inflammation in atherosclerosis
Xing, Y., & Lin, X. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.06.016 · Cited by 147
Epidermal fatty acid binding protein promotes skin inflammation induced by high-fat diet
Zhang, Y., Li, Q., Rao, E., Sun, Y., Grossmann, M. E., Morris, R. J., Cleary, M. P., & Li, B. (2015) · Immunity · doi:10.1016/j.immuni.2015.04.016 · Cited by 137
“Moreover, it is also possible that other lipid components in the HFD, such as cholesterol, can induce inflammasome activation and IL-1 production (Duewell et al., 2010).”
Winer, S., & Winer, D. A. (2012) · Immunology and Cell Biology · doi:10.1038/icb.2011.110 · Cited by 141
Biochemical regulation of the inflammasome
Dowling, J. K., & O'Neill, L. A. J. (2012) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2012.694844 · Cited by 139
Atherosclerosis and immunity: A perspective
Abdolmaleki, F., Hayat, S. M. G., Bianconi, V., Johnston, T. P., & Sahebkar, A. (2018) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2018.09.017 · Cited by 138
NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes
Hong, P., Gu, R., Li, F., Xiong, X., Liang, W., You, Z.-J., & Zhang, H. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1498-0 · Cited by 139
Role of the NLRP3 Inflammasome in Preeclampsia
Shirasuna, K., Karasawa, T., & Takahashi, M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00080 · Cited by 139
Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics
He, L., Zhang, C., Chen, Q., Wang, L., & Huang, Y. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108152 · Cited by 141
Inflammasomes: sensors of metabolic stresses for vascular inflammation
Yang, X.-F. (2013) · Frontiers in Bioscience · doi:10.2741/4127 · Cited by 134
Lysosomes Integrate Metabolic-Inflammatory Cross-talk in Primary Macrophage Inflammasome Activation
Weber, K., & Schilling, J. D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.531202 · Cited by 139
Inflammasomes and Metabolic Disease
Henao‐Mejia, J., Elinav, E., Thaiss, C. A., & Flavell, R. A. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170324 · Cited by 176
Inflammasome biology, molecular pathology and therapeutic implications
Awad, F., Assrawi, E., Louvrier, C., Jumeau, C., Georgin‐Lavialle, S., Grateau, G., Amselem, S., Giurgea, I., & Karabina, S. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.02.011 · Cited by 138
“Similarly, cholesterol crystals injected intraperitoneally induced an acute inflammation that was impaired in mice deficient in inflammasome components (Duewell et al., 2010).”
BackgroundResultLiao, J., Yang, F., Tang, Z., Yu, W., Han, Q., Hu, L., Li, Y., Guo, J., Pan, J., Ma, F., et al. (2019) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2019.02.069 · Cited by 134
NLRP3 Inflammasome: Checkpoint Connecting Innate and Adaptive Immunity in Autoimmune Diseases
Zhang, Y., Yang, W., Li, W., & Zhao, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.732933 · Cited by 142
Zhang, X., McDonald, J. G., Aryal, B. K., Canfrán‐Duque, A., Goldberg, E. L., Araldi, E., Ding, W., Fan, Y., Thompson, B. M., Singh, A. K., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2107682118 · Cited by 136
Monocyte heterogeneity in human cardiovascular disease
Zawada, A. M., Rogacev, K. S., Schirmer, S. H., Sester, M., Böhm, M., Fliser, D., & Heine, G. H. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.07.001 · Cited by 132
Lin, L., Xu, L., Lv, W., Han, L., Xiang, Y., Fu, L., Jin, M., Zhou, R., Chen, H., & Zhang, A. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007795 · Cited by 131
Shi, H., Zhang, Z., Wang, X., Li, R., Hou, W., Bi, W., & Zhang, X. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.06.060 · Cited by 132
Cyclooxygenase‐2 Regulates NLRP3 Inflammasome‐Derived IL‐1β Production
Hua, K., Chou, J., Ka, S., Tasi, Y., Chen, A., Wu, S., Chiu, H., Wong, W.-T., Wang, Y., Tsai, C., et al. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24815 · Cited by 135
“…development of disease, including pathogen infection (Kanneganti et al., 2006), type 2 diabetes mellitus (Schroder et al., 2010), atherosclerosis (Duewell et al., 2010), obesity (Vandanmagsar et al., 2011), silicosis (Hornung et al., 2008), Alzheimer’s disease (Halle et al., 2008), gout…”
BackgroundP2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation
Kuang, P., Liu, L.-S., Wei, D., Lv, Y.-C., Wang, G., Xiong, W., Wang, X., Altaf, A., Wang, L., He, D., et al. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2129 · Cited by 139
Effect of Statins on Cholesterol Crystallization and Atherosclerotic Plaque Stabilization
Abela, G. S., Vedre, A., Janoudi, A., Huang, R., Durga, S., & Tamhane, U. U. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.02.336 · Cited by 131
Self-citationThacker, S. G., Zarzour, A., Chen, Y., Alçiçek, M. S., Freeman, L. A., Sviridov, D. O., Demosky, S. J., & Remaley, A. T. (2016) · Immunology · doi:10.1111/imm.12638 · Cited by 135
Liu, X., Pichulik, T., Wolz, O., Dang, T., Stutz, A., Dillen, C. A., Garcia, M. D., Kraus, H., Dickhöfer, S., Daiber, E., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.01.017 · Cited by 137
Self-citationER Stress Activates the NLRP3 Inflammasome: A Novel Mechanism of Atherosclerosis
Chen, X., Guo, X.-C., Ge, Q., Zhao, Y., Mu, H., & Zhang, J. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/3462530 · Cited by 135
Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues
Sherratt, S. C. R., Libby, P., Budoff, M. J., Bhatt, D. L., & Mason, R. P. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01075-x · Cited by 156
Interleukin-1, inflammasomes, autoinflammation and the skin
Contassot, E., Beer, H.-D., & French, L. E. (2012) · Swiss Medical Weekly · doi:10.4414/smw.2012.13590 · Cited by 130
Macrophage activation in human diseases
Schultze, J. L., Schmieder, A., & Goerdt, S. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.07.003 · Cited by 134
Inflammasomes as therapeutic targets for A lzheimer's disease
White, C., Lawrence, C. B., Brough, D., & Rivers‐Auty, J. (2016) · Brain Pathology · doi:10.1111/bpa.12478 · Cited by 136
“The latter encompasses large sterile particulate matter, including crystals of monosodium urate and calcium pyrophosphate dihydrate, central to gout and pseudogout pathology respectively, and cholesterol crystals, involved in atherosclerosis (41).”
BackgroundYin, Y., Zhou, Z., Liu, W., Chang, Q., Sun, G., & Dai, Y. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.01.001 · Cited by 131
Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration
Tosello-Trampont, A., Surette, F. A., Ewald, S. E., & Hahn, Y. S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00301 · Cited by 134
PCSK9 inhibition and inflammation: A narrative review
Ruscica, M., Tokgözoğlu, L. S., Corsini, A., & Sirtori, C. R. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.07.015 · Cited by 133
Nlrp2, a Maternal Effect Gene Required for Early Embryonic Development in the Mouse
Peng, H., Chang, B., Lu, C., Su, J., Wu, Y., Lv, P., Wang, Y., Liu, J., Zhang, B., Quan, F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030344 · Cited by 127
Uromodulin Triggers IL-1β–Dependent Innate Immunity via the NLRP3 Inflammasome
Darisipudi, M. N., Thomasová, D., Mulay, S. R., Brech, D., Noeßner, E., Liapis, H., & Anders, H. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012040338 · Cited by 129
Danger Signals in the Initiation of the Inflammatory Response after Myocardial Infarction
de Haan, J. J., Smeets, M. B., Pasterkamp, G., & Arslan, F. (2013) · Mediators of Inflammation · doi:10.1155/2013/206039 · Cited by 139
McClean, C. M., & Tobin, D. M. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw068 · Cited by 135
Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1 β Production
Tőzsér, J., & Benkő, S. (2016) · Mediators of Inflammation · doi:10.1155/2016/5460302 · Cited by 129
Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction
Zhang, Y., Lv, X., Hu, Z., Ye, X., Zheng, X., Ding, Y., Xie, P., & Liu, Q. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.308 · Cited by 131
Liu, B., Li, X., Yu, H. V., Shi, X., Zhou, Y., Alvarez, S., Naldrett, M. J., Kachman, S. D., Ro, S., Sun, X., et al. (2021) · Theranostics · doi:10.7150/thno.60265 · Cited by 137
Shin, M. S., Kang, Y., Lee, N., Wahl, E. R., Kim, S., Kang, K. S., Lazova, R. Z., & Kang, I. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201195 · Cited by 127
Davies, R. W., Wells, G. A., Stewart, A. F. R., Erdmann, J., Shah, S. H., Ferguson, J. F., Hall, A. S., Anand, S. S., Burnett, M. S., Epstein, S. E., et al. (2012) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.111.961243 · Cited by 129
Feng, H., Gu, J., Gou, F., Huang, W. G., Gao, C., Chen, G., Long, Y., Zhou, X., Yang, M., Liu, S., et al. (2016) · Journal of Diabetes Research · doi:10.1155/2016/6973175 · Cited by 128
Macrophages and Cardiovascular Health
Frodermann, V., & Nahrendorf, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00068.2017 · Cited by 128
“Cholesterol crystals also potently activate the inflammasome, resulting in strong IL-1 responses (91) that further promote local inflammation.”
BackgroundLiu, W., Östberg, N. K., Yalçınkaya, M., Dou, H., Endo‐Umeda, K., Tang, Y., Hou, X., Xiao, T., Fidler, T. P., Abramowicz, S., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155724 · Cited by 130
IL-1 family cytokines in inflammation and immunity
Garlanda, C., Ceglie, I. D., & Jaillon, S. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01358-8 · Cited by 153
Cipolletta, D., Kolodin, D., Benoist, C. O., & Mathis, D. J. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.06.002 · Cited by 127
“Previous studies have demonstrated that cholesterol or similar crystals cause Nlrp3 inflammasome activation in macrophages found in atherosclerotic lesions [36,37].”
BackgroundMoroni, F., Ammirati, E., Norata, G. D., Magnoni, M., & Camici, P. G. (2019) · Mediators of Inflammation · doi:10.1155/2019/7434376 · Cited by 129
Kim, H., Kumar, S., Kang, D. W., Jo, H., & Park, J. (2020) · ACS Nano · doi:10.1021/acsnano.9b08216 · Cited by 127
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death
Bu, L.-L., Yuan, H., Xie, L., Guo, M.-H., Liao, D., & Zheng, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015160 · Cited by 133
Mitochondrial DNA damage and atherosclerosis
Yu, E. P. K., & Bennett, M. R. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.06.008 · Cited by 124
“Importantly NLRP3 inflammasome activation and increased IL1β release may promote atherosclerosis [52].”
BackgroundImmunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126
Intracellular sensing of microbes and danger signals by the inflammasomes
Horvath, G. L., Schrum, J. E., Nardo, C. M. D., & Latz, E. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01050.x · Cited by 127
Self-citationProatherogenic Conditions Promote Autoimmune T Helper 17 Cell Responses In Vivo
Lim, H., Kim, Y. U., Sun, H., Lee, J. H., Reynolds, J. M., Hanabuchi, S., Wu, H., Teng, B.-B., & Chung, Y. (2014) · Immunity · doi:10.1016/j.immuni.2013.11.021 · Cited by 126
“For instance, a recent study demonstrated that activation of the NLRP3 inflammasome by cholesterol crystals is required for atherogenesis (Duewell et al., 2010).”
Satoh, M., Tabuchi, T., Itoh, T., & Nakamura, M. (2013) · Clinical Science · doi:10.1042/cs20130043 · Cited by 126
Bonar, S. L., Brydges, S., Mueller, J., McGeough, M. D., Peña, C., Chen, D., Grimston, S., Hickman-Brecks, C. L., Ravindran, S., McAlinden, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035979 · Cited by 130
“, an intracellular protein complex responsible for activation of caspase 1 and the subsequent processing of pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18, respectively. The NLRP3 inflammasome is activated by multiple danger-associated moieties, including ATP, glucose, monosodium urate, calcium pyrophosphate dihy…”
BackgroundAutophagy and inflammatory diseases
Jones, S. A., Mills, K. H. G., & Harris, J. (2013) · Immunology and Cell Biology · doi:10.1038/icb.2012.82 · Cited by 127
Crystal Formation in Inflammation
Franklin, B. S., Mangan, M., & Latz, E. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055539 · Cited by 125
Self-citationBiomechanical stress in coronary atherosclerosis: emerging insights from computational modelling
Thondapu, V., Bourantas, C. V., Foin, N., Jang, I., Serruys, P. W. J. C., & Barlis, P. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv689 · Cited by 125
Inflammation in the Pathophysiology and Therapy of Cardiometabolic Disease
Donath, M. Y., Meier, D. T., & Böni‐Schnetzler, M. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00002 · Cited by 135
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
