title: Endogenous ghrelin attenuates pressure overload-induced cardiac hypertrophy via a cholinergic anti-inflammatory pathway.
abstract: Cardiac hypertrophy, which is commonly caused by hypertension, is a major risk factor for heart failure and sudden death. Endogenous ghrelin has been shown to exert a beneficial effect on cardiac dysfunction and postinfarction remodeling via modulation of the autonomic nervous system. However, ghrelin's ability to attenuate cardiac hypertrophy and its potential mechanism of action are unknown. In this study, cardiac hypertrophy was induced by transverse aortic constriction in ghrelin knockout mice and their wild-type littermates. After 12 weeks, the ghrelin knockout mice showed significantly increased cardiac hypertrophy compared with wild-type mice, as evidenced by their significantly greater heart weight/tibial length ratios (9.2±1.9 versus 7.9±0.8 mg/mm), left ventricular anterior wall thickness (1.3±0.2 versus 1.0±0.2 mm), and posterior wall thickness (1.1±0.3 versus 0.9±0.1 mm). Furthermore, compared with wild-type mice, ghrelin knockout mice showed suppression of the cholinergic anti-inflammatory pathway, as indicated by reduced parasympathetic nerve activity and higher plasma interleukin-1β and interleukin-6 levels. The administration of either nicotine or ghrelin activated the cholinergic anti-inflammatory pathway and attenuated cardiac hypertrophy in ghrelin knockout mice. In conclusion, our results show that endogenous ghrelin plays a crucial role in the progression of pressure overload-induced cardiac hypertrophy via a mechanism that involves the activation of the cholinergic anti-inflammatory pathway.
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Yuanjie
authors: Y
authors: Mao
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Takeshi
authors: T
authors: Tokudome
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.). kishimot@hsp.ncvc.go.jp.
authors: Ichiro
authors: I
authors: Kishimoto
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Kentaro
authors: K
authors: Otani
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Hirohito
authors: H
authors: Nishimura
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Osamu
authors: O
authors: Yamaguchi
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Kinya
authors: K
authors: Otsu
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Mikiya
authors: M
authors: Miyazato
authors: From the Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan (Y.M., T.T., I.K., H.N., M.M., K.K.); Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute (K.O.), Department of Cardiovascular Medicine, Graduate School of Medicine (O.Y.), Osaka University, Suita, Japan; and Cardiovascular Division, King's College London British Heart Foundation Centre, London, United Kingdom (K.O.).
authors: Kenji
authors: K
authors: Kangawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D018678:Cholinergic Agents; D004195:Disease Models, Animal; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology; D011897:Random Allocation; D012016:Reference Values; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology*
chemical_list: D001286:Atropine Derivatives; D018678:Cholinergic Agents; D054439:Ghrelin; D009538:Nicotine; C006649:methylatropine
keywords: cardiomegaly; ghrelin; inflammation; mice, knockout