Endothelial dysfunction: the role of sterol regulatory element-binding protein-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome in atherosclerosis.

PURPOSE OF REVIEW

Great effort has been devoted to elucidate the molecular mechanisms by which inflammasome in macrophages contributes to atherosclerosis. Inflammasome in vascular endothelial cells and its causal relationship with endothelial dysfunction in atherosclerosis are less understood. Here, we review the recent studies of inflammasome and its activation in endothelial cells, and highlight such endothelial inflammatory response in atherosclerosis.

RECENT FINDINGS

Inflammasomes are critical effectors in innate immunity, and their activation in macrophages and the arterial wall contributes to atherogenesis. Sterol regulatory element-binding protein 2, a master regulator in cholesterol biosynthesis, can be activated in a noncanonical manner, which leads to the activation of the NOD-like receptor family pyrin domain-containing protein inflammasome in macrophages and endothelial cells. Results from in-vitro and in-vivo models suggest that sterol regulatory element-binding protein 2 is a key molecule in aggravating proinflammatory responses in endothelial cells and promoting atherosclerosis.

SUMMARY

The SREBP-induced NOD-like receptor family pyrin domain-containing protein inflammasome and its instigation of innate immunity is an important contributor to atherosclerosis. Elucidating the underlying mechanisms will expand our understanding of endothelial dysfunction and its dynamic interaction with vascular inflammation. Furthermore, targeting SREBP-inflammasome pathways can be a therapeutic strategy for attenuating atherosclerosis.