The inflammasome in myocardial injury and cardiac remodeling.

SIGNIFICANCE

An inflammatory response follows an injury of any nature, and while such a response is an attempt to promote healing, it may, itself, result in further injury.

RECENT ADVANCES

The inflammasome is a macromolecular structure recently recognized as a central mediator in the acute inflammatory response. The inflammasome senses the injury and it amplifies the response by leading to the release of powerful pro-inflammatory cytokines, interleukin-1β (IL-1β) and IL-18.

CRITICAL ISSUES

The activation of the inflammasome in the heart during ischemic and nonischemic injury represents an exaggerated response to sterile injury and promotes adverse cardiac remodeling and failure.

FUTURE DIRECTIONS

Pilot clinical trials have explored blockade of the inflammasome-derived IL-1β and have shown beneficial effects on cardiac function. Additional clinical studies testing this approach are warranted. Moreover, specific inflammasome inhibitors that are ready for clinical use are currently lacking.