Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice

The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.