Gasdermin D Mediates Inflammation-Induced Defects in Reverse Cholesterol Transport and Promotes Atherosclerosis.

ABSTRACT: Activation of inflammasomes, such as Nlrp3 and AIM2, can exacerbate atherosclerosis in mice and humans. Gasdermin D (GsdmD) serves as a final executor of inflammasome activity, by generating membrane pores for the release of mature Interleukin-1beta (IL-1β). Inflammation dampens reverse cholesterol transport (RCT) and promotes atherogenesis, while anti-IL-1β antibodies were shown to reduce cardiovascular disease in humans. Though Nlrp3/AIM2 and IL-1β nexus is an emerging atherogenic pathway, the direct role of GsdmD in atherosclerosis is not yet fully clear. Here, we used in vivo Nlrp3 inflammasome activation to show that the GsdmD^-/- mice release ∼80% less IL-1β vs. Wild type (WT) mice. The GsdmD^-/- macrophages were more resistant to Nlrp3 inflammasome mediate

SUBMITTER: Opoku E 

PROVIDER: S-EPMC8355565 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature