Rationale: Over 50% of heart failure patients have preserved, rather than reduced ejection fraction (HFpEF vs. HFrEF). Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF. Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model.Methods and Results: By combining the age, long-term high-fat diet and desoxycorticosterone pivalate challenge in a mouse model we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of interleukin (IL)-1β/IL-18, and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate (β-OHB) level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokines-triggered mitochondrial dysfunction and fibrosis. Moreover, β-OHB downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of citrate synthase and inhibition of fatty acid uptake. Conclusions: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis which can be ameliorated by promoting β-OHB abundance.

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In this study, we report a novel method to synthesize hexagonal boron nitride nanosheets (BNNSs) using a ball‐milled mixture of ammonium fluoroborate and sodium borohydride as precursor, under an ammonia atmosphere. The detailed morphological and structural investigations of the BNNSs are carried out by means of scanning electron microscopy, transmission electron microscopy (TEM), and high‐resolution TEM, and detailed formation process of the BNNSs is proposed. We further utilize the BNNSs and acid‐treated BNNSs (ATBNNSs) as nanofillers to fabricate a series of epoxy nanocomposites and study their varied thermal properties. The results indicate that the surface treatment and different fractions of BNNSs can discriminatively influence the thermal properties of epoxy nanocomposites. We also estimate the thermal conductivity channel thresholds with different ATBNNSs and BNNSs fractions. Through this work, an understanding of the interface treatment and filler fraction effects on thermal properties of epoxy nanocomposites is obtained. POLYM. COMPOS., 35:1707–1715, 2014. © 2013 Society of Plastics Engineers