Inflammasomes, neutrophil extracellular traps, and cholesterol
Activation of macrophage inflammasomes leads to interleukin (IL)-1β and IL-18 secretion and promotes atherosclerosis and its complications in mice and humans. However, the specific role and underlying mechanisms of the inflammasome in atherogenesis are topics of active research. Several studies in h...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520325839 |
| _version_ | 1818983340675432448 |
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| author | Alan R. Tall Marit Westerterp |
| author_facet | Alan R. Tall Marit Westerterp |
| author_sort | Alan R. Tall |
| collection | DOAJ |
| description | Activation of macrophage inflammasomes leads to interleukin (IL)-1β and IL-18 secretion and promotes atherosclerosis and its complications in mice and humans. However, the specific role and underlying mechanisms of the inflammasome in atherogenesis are topics of active research. Several studies in hyperlipidemic mouse models found that the NOD-like receptor protein 3 (NLRP3) inflammasome contributes to atherosclerosis, but recent work suggests that a second hit, such as defective cholesterol efflux or accumulation of oxidized mitochondrial DNA, may be required for significant inflammasome activation. Cholesterol crystal uptake or formation in lysosomes may damage membranes and activate NLRP3 inflammasomes. Alternatively, plasma or ER membrane cholesterol accumulation may condition macrophages for inflammasome activation in the presence of danger-associated molecular patterns, such as oxidized LDL. Inflammasome activation in macrophages or neutrophils leads to gasdermin-D cleavage that induces membrane pore formation, releasing IL-1β and IL-18, and eventuating in pyroptosis or neutrophil extracellular trap formation (NETosis). In humans, inflammasome activation and NETosis may contribute to atherosclerotic plaque erosion and thrombosis, especially in patients with type 2 diabetes, chronic kidney disease, or clonal hematopoiesis. Suppression of the inflammasome by activation of cholesterol efflux or by direct inhibition of inflammasome components may benefit patients with CVD and underlying susceptibility to inflammasome activation. |
| first_indexed | 2024-12-20T18:01:33Z |
| format | Article |
| id | doaj.art-77453c3d67524668a5d9d7124a040b66 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T18:01:33Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-77453c3d67524668a5d9d7124a040b662022-12-21T19:30:37ZengElsevierJournal of Lipid Research0022-22752019-04-01604721727Inflammasomes, neutrophil extracellular traps, and cholesterolAlan R. Tall0Marit Westerterp1To whom correspondence should be addressed.; Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032; To whom correspondence should be addressed.To whom correspondence should be addressed.; Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; To whom correspondence should be addressed.Activation of macrophage inflammasomes leads to interleukin (IL)-1β and IL-18 secretion and promotes atherosclerosis and its complications in mice and humans. However, the specific role and underlying mechanisms of the inflammasome in atherogenesis are topics of active research. Several studies in hyperlipidemic mouse models found that the NOD-like receptor protein 3 (NLRP3) inflammasome contributes to atherosclerosis, but recent work suggests that a second hit, such as defective cholesterol efflux or accumulation of oxidized mitochondrial DNA, may be required for significant inflammasome activation. Cholesterol crystal uptake or formation in lysosomes may damage membranes and activate NLRP3 inflammasomes. Alternatively, plasma or ER membrane cholesterol accumulation may condition macrophages for inflammasome activation in the presence of danger-associated molecular patterns, such as oxidized LDL. Inflammasome activation in macrophages or neutrophils leads to gasdermin-D cleavage that induces membrane pore formation, releasing IL-1β and IL-18, and eventuating in pyroptosis or neutrophil extracellular trap formation (NETosis). In humans, inflammasome activation and NETosis may contribute to atherosclerotic plaque erosion and thrombosis, especially in patients with type 2 diabetes, chronic kidney disease, or clonal hematopoiesis. Suppression of the inflammasome by activation of cholesterol efflux or by direct inhibition of inflammasome components may benefit patients with CVD and underlying susceptibility to inflammasome activation.http://www.sciencedirect.com/science/article/pii/S0022227520325839adenosine 5′-triphosphate binding cassette transportershigh density lipoproteinoxidized lipidsatherosclerosismacrophages |
| spellingShingle | Alan R. Tall Marit Westerterp Inflammasomes, neutrophil extracellular traps, and cholesterol Journal of Lipid Research adenosine 5′-triphosphate binding cassette transporters high density lipoprotein oxidized lipids atherosclerosis macrophages |
| title | Inflammasomes, neutrophil extracellular traps, and cholesterol |
| title_full | Inflammasomes, neutrophil extracellular traps, and cholesterol |
| title_fullStr | Inflammasomes, neutrophil extracellular traps, and cholesterol |
| title_full_unstemmed | Inflammasomes, neutrophil extracellular traps, and cholesterol |
| title_short | Inflammasomes, neutrophil extracellular traps, and cholesterol |
| title_sort | inflammasomes neutrophil extracellular traps and cholesterol |
| topic | adenosine 5′-triphosphate binding cassette transporters high density lipoprotein oxidized lipids atherosclerosis macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520325839 |
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