Cardiovascular pathobiology of inflammasomes: inflammatory machinery and beyond.

SIGNIFICANCE: In response to infection or cellular stress, inflammasomes are assembled and activated to mediate host defense and to initiate or promote the development of different diseases, in particular, autoinflammatory diseases and chronic degenerative diseases. Understanding of inflammasomes and related physiological and pathological relevance to the cardiovascular system will open a new chapter on the pathogenesis of inflammation and related diseases and will help develop novel therapeutic strategies for prevention or treatment of cardiovascular diseases. RECENT ADVANCES: The inflammasome, in particular the nucleotide oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome, has been recently recognized as a fundamental mechanism to mediate or promote the pathogenesis of degenerative diseases. Some important mechanisms responsible for NLRP3 inflammasome activation have been proposed and many molecular targets associated with this inflammasome activation are shown to be the possible candidates of therapeutic targets for treatment of cardiovascular diseases. CRITICAL ISSUES: The concepts that NLRP3 inflammasome activation occurs just in immune cells or phagocytes and that its role is only for the inflammatory progression of cardiovascular diseases are oversimplified. A large body of other cell types are capable of NLRP3 inflammasome activation, and many uncanonical effects of this inflammasome may also be implicated in the development of cardiovascular diseases, which are discussed in a great detail by this Forum. FUTURE DIRECTIONS: More mechanistic and translational studies will rapidly widen the horizon of knowledge on NLRP3 inflammasome activation and regulation, which may help develop novel effective therapeutic strategies to target this inflammasome for treatment or prevention of cardiovascular diseases.