Genetic inhibition of CARD9 accelerates the development of experimental atherosclerosis through CD36 dependent-defective autophagy

Macrophage-mediated innate immune responses contribute to the initiation, progression and complications of atherosclerosis. However, the underlying pathways linking activation of macrophages to atherosclerotic plaque develoment are still poorly understood. We hypothesized that activation of caspase recruitment-domain containing protein 9 (CARD9) plays a determinant role in pro-atherogenic responses in macrophages. Transcriptomic analysis of human monocytes isolated from CARD9-deficient patients confirmed the pathogenic signature identified in several murine models: increased production of pro-inflammatory cytokines, improved lipid uptake, higher cell death susceptibility and defective autophagy. Overall design: RNA-seq analysis from circulating monocytes from CARD9 deficient patients (n=3) with those of controls.