Double-Strand DNA Sensing Aim2 Inflammasome Regulates Atherosclerotic Plaque Vulnerability
| Autor: | Sanne L. Maas, Nicole Paulin, Christian Weber, Teresa Fernandes-Alnemri, Maik Drechsler, Yvonne Döring, Joana R. Viola, Renske J. de Jong, Oliver Soehnlein |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammasomes Mice Knockout ApoE Inflammation 030204 cardiovascular system & hematology Proinflammatory cytokine 03 medical and health sciences AIM2 Mice 0302 clinical medicine Physiology (medical) medicine Animals Humans RNA Small Interfering business.industry Fibrous cap Pattern recognition receptor Inflammasome Neutrophil extracellular traps DNA Atherosclerosis Plaque Atherosclerotic 3. Good health DNA-Binding Proteins Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cancer research medicine.symptom Cardiology and Cardiovascular Medicine business Inflammasome complex medicine.drug |
| Zdroj: | Circulation |
| ISSN: | 1524-4539 |
| Popis: | Atherosclerosis, a lipid-driven sterile inflammatory disease of large arteries, and its sequelae such as myocardial infarction and stroke are the most frequent cause of death worldwide. Although atherogenesis is characterized by the accumulation of inflammatory myeloid cells, destabilization of atherosclerotic lesions is dominated by necrotic core expansion and thinning of the fibrous cap. Sterile inflammation is typically induced by host-derived damage-associated molecular patterns that are sensed by pattern recognition receptors. In recent years, cytosolic pattern recognition receptors like the NLRP3 inflammasome have been connected to atherosclerosis, because these can recognize (altered) self-structures such as lesional cholesterol crystals.1 Consequently, the inflammasome complex assembles promoting the release of proinflammatory cytokines interleukin-1β (IL1β) and interleukin-18 (IL18). The recent CANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) lends strong support toward the importance of IL1β in the context of atherosclerosis because therapeutic IL1β neutralization in patients with established atherosclerotic disease revealed a significant reduction in the incidence of a recurrent cardiovascular event.2 Progression of atherosclerosis is characterized by the accumulation of dead cells. Several cell death pathways permitting release of nuclear double-stranded (ds) DNA have been identified including necrosis and release of neutrophil extracellular traps. The amount of extracellular DNA correlates with the risk of cardiovascular events.3 Cytosolic dsDNA can be identified by Absent in melanoma 2 (Aim2) inflammasome leading to the release of IL1β and IL18.4 It is noteworthy that Aim2 has recently been identified in human atherosclerotic lesions in proximity to necrotic cores.5 Here, we study the inflammatory cascade on dsDNA recognition in the context of atherosclerosis by genetically deleting or therapeutically … |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|