Jian Zhang1, Liming Yu2, Yinli Xu2, Yu Liu2, Zhi Li2, Xiaodong Xue2, Song Wan3, Huishan Wang4. 1. Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, No.83, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, China; Department of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. 2. Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, No.83, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, China. 3. Department of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. Electronic address: swan@cuhk.edu.hk. 4. Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, No.83, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, China. Electronic address: huishanw@126.com.
Abstract
BACKGROUND: Myocardial infarction (MI) is one of the most common causes of cardiac morbidity and mortality. Many evidences suggest that hypothermia have a more pronounced impact as an adjunctive therapy for MI to reduce infarct size. However, the function of long non-coding RNAs (lncRNA) in therapeutic hypothermia for MI remains poorly understood. METHODS: In this study, we investigated the expression of lncRNA-UIHTC (upregulated in hypothermia treated cardiomyocytes, NONHSAT094064) in ischemic heart tissues. To investigate its function, overexpression of UIHTC was performed by adeno-associated virus vectors after MI model in rat. RESULTS: lncRNA-UIHTC was upregulated in ischemic or injury cardiomyocytes. Overexpression of lncRNA-UIHTC in peri-infarction attenuated cardiac dysfunction in vivo. Mechanistically, lncRNA-UIHTC enhanced the mitochondrial function via upregulation of PGC1α. Moreover, when we knocked down PGC1α, the mitochondrial maximal oxygen consumption and ATP levels enhanced by overexpression of UIHTC were nearly completely restored. CONCLUSIONS: Altogether we have provided a new mechanism whereby hypothermia protected heart against ischemic via lncRNA-UIHTC. The UIHTC provided a new potential therapeutic target for MI but prevented the complications of hypothermia.
BACKGROUND:Myocardial infarction (MI) is one of the most common causes of cardiac morbidity and mortality. Many evidences suggest that hypothermia have a more pronounced impact as an adjunctive therapy for MI to reduce infarct size. However, the function of long non-coding RNAs (lncRNA) in therapeutic hypothermia for MI remains poorly understood. METHODS: In this study, we investigated the expression of lncRNA-UIHTC (upregulated in hypothermia treated cardiomyocytes, NONHSAT094064) in ischemic heart tissues. To investigate its function, overexpression of UIHTC was performed by adeno-associated virus vectors after MI model in rat. RESULTS: lncRNA-UIHTC was upregulated in ischemic or injury cardiomyocytes. Overexpression of lncRNA-UIHTC in peri-infarction attenuated cardiac dysfunction in vivo. Mechanistically, lncRNA-UIHTC enhanced the mitochondrial function via upregulation of PGC1α. Moreover, when we knocked down PGC1α, the mitochondrial maximal oxygen consumption and ATP levels enhanced by overexpression of UIHTC were nearly completely restored. CONCLUSIONS: Altogether we have provided a new mechanism whereby hypothermia protected heart against ischemic via lncRNA-UIHTC. The UIHTC provided a new potential therapeutic target for MI but prevented the complications of hypothermia.