RhoE and Inflammation in Myocardial Infarction

Abstract

Cardiac inflammatory response after myocardial infarction (MI) is essential to clear necrotic myocardium for cardiac healing, while excessive and prolonged inflammation extends the infarction and promotes adverse cardiac remodeling. NF-κB is the pivot regulator upstream of inflammatory response. Overaction of NF-κB exaggerates inflammation and contributes to detrimental outcomes of MI as well as other inflammatory diseases.

Here we report RhoE as a negative inflammatory mediator by specifically inhibiting NF-κB. RhoE-deficient mice show overactivation of NF-κB in heart and develop excessive inflammation after MI. Mechanistically, RhoE interacts with p65 and p50 in cytosol and inhibits their nuclear translocation. RhoE also occupies the dimerization domain of p65 to impede the formation of p65/p50 heterodimer. Finally, we show that cardiac-specific RhoE overexpression restrains post-MI inflammation and improves cardiac function and survival. These findings identify RhoE as an important mediator of NF-κB-induced inflammation, and therefore, RhoE may serve as a potential anti-inflammatory target to achieve beneficial consequences.