title: High fructose causes cardiac hypertrophy via mitochondrial signaling pathway.
abstract: High fructose diet can cause cardiac hypertrophy and oxidative stress is a key mediator for myocardial hypertrophy. Disruption of cystic fibrosis transmembrane conductance regulator (CFTR) leads to oxidative stress. This study aims to reveal mitochondrial oxidative stress-related signaling pathway in high fructose-induced cardiac hypertrophy. Mice were fed high fructose to develop cardiac hypertrophy. Fructose and H2O2were used to induce cardiomyocyte hypertrophy in vitro. Mitochondria-targeted antioxidant SkQ1 was applied to investigate the possible role of mitochondrial reactive oxygen species (ROS). CFTR silence was performed to detect the role of CFTR in high fructose-induced myocardial hypertrophy. ROS, glutathione (GSH), mitochondrial function and hypertrophic markers were measured. We confirmed that long-term high fructose diet caused cardiac hypertrophy and diastolic dysfunction and elevated mitochondrial ROS. However, SkQ1 administration prevented heart hypertrophy and mitochondrial oxidative stress. Cadiomyocytes incubated with fructose or H2O2exhibited significantly increased cell areas but SkQ1 treatment ameliorated cardiomyocyte hypertrophy induced by high fructose or H2O2in vitro. Those results revealed that the underlying mechanism for high fructose-induced heart hypertrophy was attributed to mitochondrial oxidative stress. Moreover, CFTR expression was decreased by high fructose intervention and CFTR silence resulted in an increase in mitochondrial ROS, which suggested high fructose diet affected mitochondrial oxidative stress by regulating CFTR expression. Electron transport chain impairment might be related to mitochondrial oxidative damage. In conclusion, our findings indicated that mitochondrial oxidative stress plays a central role in pathogenesis of high fructose-induced cardiac hypertrophy. High fructose decreases CFTR expression to regulate mitochondrial oxidative stress.
authors.affiliation: Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's Republic of China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's Republic of China.
authors.forename: Yan-Hai
authors.initials: YH
authors.lastname: Meng
authors.affiliation: Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chang
authors.affiliation: Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's Republic of China.
authors.forename: Rong-Yuan
authors.initials: RY
authors.lastname: Zhang
authors.affiliation: Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
keywords: Fructose; cardiac hypertrophy; cystic fibrosis transmembrane conductance regulator; mitochondria; oxidative stress