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Ketone Bodies Rescue Mitochondrial Dysfunction Via Epigenetic Remodeling 1 Methods 2 Human cardiac specimens and ethics statement 2 In vivo model 2 In vitro assays 3 Statistical analysis 3 Results 4 Cardiac ischemic injury leads to a specific histone modification in patients, mice, and cells 4 Ischemic insult leads to apoptosis and mitochondrial dysfunction in vitro 5 BHB counteracts the histone modifications induced by ischemia, both in vitro and in vivo 5 BHB protects against ischemia-induced mitochondrial apoptosis 5 BHB treatment in vivo protects against postischemic HF 8 BHB protects cardiac mitochondria from MI-induced organelle dysfunction preventing PGC1α down-regulation 11 H3_K27me2K36me1 mediates the maladaptive transcriptional repression of PGC1α during ischemia 11 Discussion 13 Study limitations 14 Conclusions 14 Acknowledgments 14 Funding Support and Author Disclosures 14 References 15

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nonfiction