Xiaohan Xu1, Linjie Si1, Jing Xu1, Chenlong Yi1, Fang Wang1, Weijuan Gu1, Yuqing Zhang1, Xiaowei Wang1. 1. 1 Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China ; 2 Institute of Integrated Medicine, Nanjing Medical University, Nanjing 210029, China ; 3 Department of Intensive Care Medicine, The First People's Hospital of Yancheng, Yancheng 224005, China ; 4 Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China ; 5 Department of Cardiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China.
Abstract
BACKGROUND: Activated interleukin (IL)-1β signaling pathway is closely associated with pathological cardiac hypertrophy. This study investigated whether asiatic acid (AA) could inhibit IL-1β-related hypertrophic signaling, and thus suppressing the development of cardiac hypertrophy. METHODS: Transverse aortic constriction (TAC) induced cardiac hypertrophy in C57BL/6 mice and cultured neonatal cardiac myocytes stimulated with IL-1β were used to evaluate the role of AA in cardiac hypertrophy. The expression of atrial natriuretic peptide (ANP) was evaluated by quantitative polymerase chain reaction (qPCR) and the nuclear factor (NF)-κB binding activity was measured by electrophoretic mobility shift assays (EMSA). RESULTS: AA pretreatment significantly attenuated the IL-1β-induced hypertrophic response of cardiomyocytes as reflected by reduction in the cardiomyocyte surface area and the inhibition of ANP mRNA expression. The protective effect of AA on IL-1β-stimulated cardiomyocytes was associated with the reduction of NF-κB binding activity. In addition, AA prevented TAC-induced cardiac hypertrophy in vivo. It was found that AA markedly reduced the excessive expression of IL-1β and ANP, and inhibited the activation of NF-κB in the hypertrophic myocardium. CONCLUSIONS: Our data suggest that AA may be a novel therapeutic agent for cardiac hypertrophy. The inhibition of IL-1β-activated NF-κB signaling may be the mechanism through which AA prevents cardiac hypertrophy.
BACKGROUND: Activated interleukin (IL)-1β signaling pathway is closely associated with pathological cardiac hypertrophy. This study investigated whether asiatic acid (AA) could inhibit IL-1β-related hypertrophic signaling, and thus suppressing the development of cardiac hypertrophy. METHODS: Transverse aortic constriction (TAC) induced cardiac hypertrophy in C57BL/6 mice and cultured neonatal cardiac myocytes stimulated with IL-1β were used to evaluate the role of AA in cardiac hypertrophy. The expression of atrial natriuretic peptide (ANP) was evaluated by quantitative polymerase chain reaction (qPCR) and the nuclear factor (NF)-κB binding activity was measured by electrophoretic mobility shift assays (EMSA). RESULTS: AA pretreatment significantly attenuated the IL-1β-induced hypertrophic response of cardiomyocytes as reflected by reduction in the cardiomyocyte surface area and the inhibition of ANP mRNA expression. The protective effect of AA on IL-1β-stimulated cardiomyocytes was associated with the reduction of NF-κB binding activity. In addition, AA prevented TAC-induced cardiac hypertrophy in vivo. It was found that AA markedly reduced the excessive expression of IL-1β and ANP, and inhibited the activation of NF-κB in the hypertrophic myocardium. CONCLUSIONS: Our data suggest that AA may be a novel therapeutic agent for cardiac hypertrophy. The inhibition of IL-1β-activated NF-κB signaling may be the mechanism through which AA prevents cardiac hypertrophy.
Authors: Rajanikant G Krishnamurthy; Marie-Claude Senut; Daniel Zemke; Jiangyong Min; Mark B Frenkel; Eric J Greenberg; Seong-Woon Yu; Nick Ahn; John Goudreau; Mounzer Kassab; Kiran S Panickar; Arshad Majid Journal: J Neurosci Res Date: 2009-08-15 Impact factor: 4.164