Editors' ChoiceCardiovascular Disease

Burning Heart

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Science Translational Medicine  07 Dec 2011:
Vol. 3, Issue 112, pp. 112ec200
DOI: 10.1126/scitranslmed.3003539

In the setting of an acute heart attack, the inflammasome network of proteins ignites an inflammatory response, which can weaken the heart and cause total heart failure. Inflammation is the natural biologic response to combat harmful stimuli and protect the body; its etymologic roots stem from the Latin word inflammare, which means “to set on fire.” The rock band Survivor sums up the process well: “In the burning heart just about to burst, There’s a quest for answers, an unquenchable thirst.” In a new article by Mezzaroma et al., the authors search for the answers to how the inflammasome contributes to heart failure after myocardial infarction (MI).

In a mouse model of cardiac ischemia, the authors found an increase in caspase-1 activity after MI, as well as an abundance of the structural component of the inflammasome known as the ASC (apoptosis speck-like protein containing a caspase-recruitment domain). ASC overexpression was confirmed to occur in various heart cells (cardiomyoctyes, leukocytes, fibroblasts, endothelial cells) in mice with acute MI compared with healthy, noninfarcted mice. Inhibiting components of the inflammasome, specifically P2X7, a receptor that is activated by adenosine triphosphate and other cellular debris, and cryopyrin, a protein that is involved with caspase-1 activation, using both small-molecule drugs and small interfering RNAs, prevented caspase-1 activity and cell death in cardiomyocytes. This suggests that directly inhibiting components of the inflammasome may be sufficient to blunt caspase-1 activity during a heart attack, thus reducing cell death and heart failure.

The treatment options offered by Mezzaroma and colleagues may be considered a new way to cool down the burning, post-MI heart. Although this article does not address every question related to the inflammasome, it is an important step forward in a translational treatment targeting the inflammasome, to help reduce morbidity after a heart attack.

E. Mezzaroma et al., The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc. Natl. Acad. Sci. U.S.A. 21 November 2011 (10.1073/pnas.1108586108). [Abstract]

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