Caspase recruitment domain-containing protein 9 (CARD9) knockout reduces regional ischemia/reperfusion injury through an attenuated inflammatory response.

Ischemic heart disease remains a leading cause of morbidity and mortality in the United States. Interventional reperfusion induces further damage to the ischemic myocardium through neutrophil infiltration and acute inflammation. As caspase recruitment domain-containing protein 9 (CARD9) plays a critical role in innate immune response and inflammation, we hypothesized that CARD9 knockout would provide protection against ischemia and reperfusion (I/R) injury through attenuation of acute inflammatory responses.

CARD9 as a potential target in cardiovascular disease.

Systemic inflammation and localized macrophage infiltration have been implicated in cardiovascular pathologies, including coronary artery disease, carotid atherosclerosis, heart failure, obesity-associated heart dysfunction, and cardiac fibrosis. Inflammation induces macrophage infiltration and activation and release of cytokines and chemokines, causing tissue dysfunction by instigating a positive feedback loop that further propagates inflammation. Cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) is a protein expressed primarily by dendritic cells, neutrophils, and macrophages, in which it mediates cytokine secretion.

CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.

Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months.