The NLRP3 Inflammasome as a promising target for Coronary Artery Disease: Current and Pipeline NLRP3 Inhibitors

Coronary Artery Disease (CAD) represents a major health burden worldwide. It is driven by chronic inflammation of the arterial vasculature supplying the heart, in response to pro-inflammatory assaults such as high LDL cholesterol. The resultant atherosclerosis can cause occlusive disease and acute cardiovascular events. The pro-inflammatory cytokine, IL-1β is a central component of this inflammatory response and signalling is activated and amplified by the NLRP3 inflammasome. Rational therapeutic targeting of these mediators could modify atherosclerotic disease progression; myocardial remodelling and CAD patient outcomes. Here we discuss promising current and pipeline inhibitors of the NLRP3 inflammasome family.

Keywords: Coronary artery disease; Atherosclerosis; IL-1β; NLRP3 inflammasome; IL-1β inhibitors; NLRP3 inhibitors

Abbreviations: CAD: Coronary Artery Disease; PCI: Percutaneous Coronary Intervention; CABG: Coronary Artery Bypass Graft; PAMPS: Pathogen- Associated Molecular Pattern Molecules; DAMPS: Damage-Associated Molecular Patterns; NLRP3 (NOD [Nucleotide Oligomerization Domain]-, LRR [Leucine-Rich Repeat]-, And PYD [Pyrin Domain]-Containing Protein 3); ASC: Apoptosis-Associated Speck-Like Protein Containing A CARD; NLRC4: NLR Family CARD Domain Containing 4; AMI: Acute Myocardial Infarction.