Nlrp3 inflammasome as a common denominator of atherosclerosis and abdominal aortic aneurysm

Abstract

Atherosclerosis and abdominal aortic aneurysm (AAA) are multifactorial diseases characterized by inflammatory cell infiltration, matrix degradation, and thrombosis in the arterial wall. Although there are some differences between atherosclerosis and AAA, inflammation is a prominent common feature of these disorders. The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a cytosolic multiprotein complex that activates caspase-1 and regulates the release of proinflammatory cytokines interleukin (IL)-1β and IL-18, as well as the induction of lytic cell death, termed pyroptosis, thereby leading to inflammation. Previous experimental and clinical studies have demonstrated that inflammation in atherosclerosis and AAA is mediated primarily through the NLRP3 inflammasome. Furthermore, recent results of the Canakinumab Anti-inflammatory Thrombosis and Outcome Study (CANTOS) showed that IL-1β inhibition reduces systemic inflammation and prevents atherothrombotic events; this supports the concept that the NLRP3 inflammasome is a promising therapeutic target for cardiovascular diseases, including atherosclerosis and AAA. This review summarizes current knowledge with a focus on the role of the NLRP3 inflammasome in atherosclerosis and AAA, and discusses the prospects of NLRP3 inflammasome-targeted therapy.