Genetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy.

ABSTRACT: Caspase recruitment-domain containing protein 9 (CARD9) is a key signaling pathway in macrophages but its role in atherosclerosis is still poorly understood. Global deletion of Card9 in Apoe^-/- mice as well as hematopoietic deletion in Ldlr^-/- mice increases atherosclerosis. The acceleration of atherosclerosis is also observed in Apoe^-/-Rag2^-/-Card9^-/- mice, ruling out a role for the adaptive immune system in the vascular phenotype of Card9 deficient mice. Card9 deficiency alters macrophage phenotype through CD36 overexpression with increased IL-1β production, increased lipid uptake, higher cell death susceptibility and defective autophagy. Rapamycin or metformin, two autophagy inducers, abolish intracellular lipid overload, restore ma

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10394049 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature