Key result
Eplerenone inhibits atrial fibrosis and macrophage infiltration in transgenic mice.
Why the study?
The impacts of eplerenone on atrial fibrosis and the underlying mechanisms in a selective atrial fibrosis mouse model were not fully understood.
Does eplerenone reduce atrial fibrosis and macrophage accumulation in mutant TGF-β1 transgenic mice?
Does eplerenone reduce atrial fibrosis and macrophage accumulation in mutant TGF-β1 transgenic mice?
Eplerenone attenuates atrial fibrosis and macrophage infiltration in a transgenic mouse model, highlighting a potential mechanism for mineralocorticoid receptor antagonists in preventing atrial structural remodeling.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for MR blockade in atrial fibrosis; leaves open translation from mouse models to human AF.
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 macrophage 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, α-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts. Finally, using a co-culture system, we showed that TGF-β1-stimulated atrial fibroblasts 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 infiltration in Tx mice. TGF-β1 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions between fibroblasts and macrophages.
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Zhang et al. (2016) studied Atrial fibrosis. Eplerenone vs. Untreated Tx mice was evaluated on Atrial fibrosis and macrophage infiltration (p=<0.05). Eplerenone significantly inhibited atrial fibrosis, macrophage infiltration, and the expression of fibrosis-related molecules in mutant TGF-β1 transgenic mice.
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