Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2015
Cardiac-specific PID1 overexpression enhances pressure overload-induced cardiac hypertrophy in mice.
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Liu Yaoqiu, Shen Yahui, Zhu Jingai, Liu Ming, Li Xing, Chen Yumei, Kong Xiangqing, Song Guixian, Qian Lingmei
Аннотация
BACKGROUND/AIMS: PID1 was originally described as an insulin sensitivity relevance protein, which is also highly expressed in heart tissue. However, its function in the heart is still to be elucidated. Thus this study aimed to investigate the role of PID1 in the heart in response to hypertrophic stimuli.
METHODS: Samples of human failing hearts from the left ventricles of dilated cardiomyopathy (DCM) patients undergoing heart transplants were collected. Transgenic mice with cardiomyocyte-specific overexpression of PID1 were generated, and cardiac hypertrophy was induced by transverse aortic constriction (TAC). The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples.
RESULTS: A significant increase in PID1 expression was observed in failing human hearts and TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway in vivo suggested that these adverse effects of PID1 were associated with the inhibition of AKT, and activation of MAPK pathway.
CONCLUSION: Under pathological conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating the Akt and MAPK pathway.
METHODS: Samples of human failing hearts from the left ventricles of dilated cardiomyopathy (DCM) patients undergoing heart transplants were collected. Transgenic mice with cardiomyocyte-specific overexpression of PID1 were generated, and cardiac hypertrophy was induced by transverse aortic constriction (TAC). The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples.
RESULTS: A significant increase in PID1 expression was observed in failing human hearts and TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway in vivo suggested that these adverse effects of PID1 were associated with the inhibition of AKT, and activation of MAPK pathway.
CONCLUSION: Under pathological conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating the Akt and MAPK pathway.
Предметные рубрики MeSH
AnimalsCardiomegalyCarrier ProteinsDisease Models, AnimalHeart FailureHeart VentriclesHumansMaleMiceMice, Inbred C57BLMice, TransgenicMitogen-Activated Protein KinasesMyocardiumMyosin Heavy ChainsPressurePromoter Regions, GeneticProto-Oncogene Proteins c-aktReal-Time Polymerase Chain ReactionSignal TransductionUltrasonographyUp-Regulation