Received July 30, 2018; Accepted December 23, 2018; Published January 19, 2019
Carmen S. Booth, Hashimoto G. Weis, Pablo Hales, Amanda H. Matherly, Lynn C. Graf 1
Abstract
Macrophages play critical roles in the promotion of myocardial infarction (MI) and the subsequent impairment of cardiac function. A variety of pro-inflammatory mediators can activate macrophages, but the pathways through which they act to activate macrophages and promote the phagocytosis of dead myocardial cells remain largely unknown. Preliminary work indicated that both Gαs and EP2 receptor deficient mice have limited mobility. Also, knockdown of EP2 receptors in macrophages can ameliorate the impairment physical activity in pressure overloaded mice, suggesting that EP2 signals produced in the working myocardium can inhibit macrophage activity, which can promote the phagocytosis of dead cardiomyocytes. This makes us suggest that macrophage EP2-PKA signals in HFshF+ mice can reduce myocardial function, and in pressure overloaded mice. PKA has been shown to inhibit polyubiquitination of mTOR in the working myocardium and is known to promote rather than inhibit myocardial hypertrophy, suggesting that EP2-PKA signals need to activate transcription of other genes that can promote, rather than inhibit autophagy. The goal of the current study is to determine whether the inhibition of EP2-PKA signaling in HFshF+IL1b+ increases the accumulation of macrophages that are Cd80+ and can promote the phagocytosis of dead cardiomyocytes. If the current study is able to accomplish this goal, it will corroborate our previous findings suggesting that inhibition of EP2-PKA signaling in macrophages can reduce myocardial function in pressure-overloaded mice.
Keywords: Macrophages; EP2-PKA; Cardio-protective; TLR ligation
Copyright © 2019 Graf, et al.
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