Inflammasome Activation in Reperfusion Injury

Abstract

With the advances in percutaneous coronary intervention technology and accompanying medical therapy, the prognosis of patients with acute coronary syndromes has greatly improved over the last decades. Still, approximately 6% of admitted patients do not survive to hospital discharge,1 and despite the implementation of rapid interventional protocols, loss of cardiac tissue, and a consecutive decrease in cardiac function is the frequent consequence of acute myocardial infarction. In addition, increasing experimental and clinical evidence demonstrates that revascularization itself triggers a harmful inflammatory response, termed ischemia-reperfusion (I/R) injury, that might contribute up to 50% of the ultimate infarction area2 and that can exert deleterious effects even beyond the initially affected perfusion territory. Since the first description of I/R injury by Jennings et al in the 1960s,3,4 a large number of studies have aimed to unravel the basic mechanisms of this complex pathophysiological process. It became evident that I/R injury is an inflammatory-driven mechanism, in part depending on the infiltration of bone marrow-derived cells and the activation of classic inflammatory pathways.5 However, none of the experimental strategies has evolved into a clinically applicable adjuvant therapy for the treatment of acute coronary syndrome-patients, demonstrating the complexity of I/R injury. Article see p 594 Recently, different components of the innate immune system, the evolutionarily ancient defense mechanism against exogenous pathogens and endogenous danger signals, were implicated in this context.6 In this issue of Circulation , Kawaguchi and coworkers from the Shinshu School of Medicine and the Jichi Medical University in Japan present comprehensive experimental data that demonstrate a critical role of the inflammasome in cardiac fibroblasts for myocardial I/R injury.7 The term “inflammasome” was coined …