Lezing 'Cholesterol efflux pathways suppress inflammasome activation, neutrophil extracellular trap formation, and atherosclerosis'

Voor wie
Studenten, Medewerkers, Alumni, Bedrijven
16-03-2018 van 11:30 tot 12:45
UGent-VIB-onderzoeksgebouw, Technologiepark 927, 9052 Zwijnaarde
Door wie
VIB-UGent Center for Inflammation Research (GE01/WE14/WE10)
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Marit Westerterp (University of Groningen, The Netherlands) will explain her work on cholesterol, inflammasomes and atherosclerosis.

The CANTOS trial indicated that pathways required for IL-1β secretion increase cardiovascular risk in humans. IL-1β and IL-18 are produced via the NLRP3 inflammasome in myeloid cells in response to excessive cholesterol accumulation, but mechanisms linking NLRP3 inflammasome activation to atherogenesis are unclear. ATP Binding Cassette A1 and G1 (ABCA1/G1) mediate cholesterol efflux to high-density-lipoprotein and Abca1/g1 deficiency in myeloid cells leads to excessive cholesterol accumulation.
Using several mouse models, we here demonstrate that myeloid Abca1/g1 deficiency activates the NLRP3 inflammasome and accelerates atherogenesis in an NLRP3 inflammasome dependent manner, which was accompanied by accumulation of neutrophil extracellular traps (NETs) in atherosclerotic plaques. Tangier Disease patients, who carry a homozygous loss-of-function mutation for ABCA1 and have increased myeloid cholesterol content, showed signs of inflammasome activation, suggesting human relevance.