The NACHT,
leucine-rich repeat (LRR), and pyrin domain (PYD)-containing
protein 3 (NLRP3)
inflammasome is an intracellular sensing
protein complex that plays a major role in innate immunity. Following tissue injury, activation of the NLRP3
inflammasome results in
cytokine production, primarily interleukin(IL)-1β and
IL-18, and, eventually, inflammatory cell death - pyroptosis. While a balanced inflammatory response favors damage resolution and tissue healing, excessive NLRP3 activation causes detrimental effects. A key involvement of the NLRP3
inflammasome has been reported across a wide range of
cardiovascular diseases (CVDs). Several pharmacological agents selectively targeting the NLRP3
inflammasome system have been developed and tested in animals and early phase human studies with overall promising results. While the NLRP3 inhibitors are in clinical development, multiple randomized trials have demonstrated the safety and efficacy of
IL-1 blockade in
atherothrombosis,
heart failure and recurrent
pericarditis. Furthermore, the non-selective NLRP3 inhibitor
colchicine has been recently shown to significantly reduce cardiovascular events in patients with chronic
coronary disease. In this review, we will outline the mechanisms driving NLRP3 assembly and activation, and discuss the pathogenetic role of the NLRP3
inflammasome in CVDs, providing an overview of the current and future therapeutic approaches targeting the NLRP3
inflammasome.