title: Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model.
abstract: A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting.
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Kuai
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.|Poisoning and Treatment Department, Beijing 307 Hospital, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.|Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Gongqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Yuezhong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D006470:Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid