FIGURE 6.

Proposed model for the deterioration of atherosclerosis by NETs. NETs induced by the various stimuli, including the nicotine, promote EGFR activity possibly through facilitating conversion of a membrane-bound EGFR ligand such as TGF-α, to its active soluble form by its proteolytic activity. Activated EGFR phosphorylates Beclin-1, thereby suppressing the Beclin-1-dependent PI3 kinase activity, which results in the suppression of an autophagy machinery. Attenuation of the autophagy activity causes enhancement of the inflammasome activity, which results in the aggravation of the atherosclerosis.