S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-kB signaling

The extracellular heterodimeric protein S100A8/A9 activates the innate immune system through activation of the receptor of advanced glycation endproducts (RAGE) and Toll-like receptors. As activation of RAGE has recently been associated with sustained myocardial inflammation and heart failure (HF) we studied the role of S100A8/A9 in the development of post-ischemic HF. Hypoxia led to sustained induction of S100A8/A9 accompanied by increased nuclear factor (NF-)kB binding activity and increased expression of pro-inflammatory cytokines in cardiac fibroblasts and macrophages. Knock-down of either S100A8/A9 or RAGE…