Wild-type p53-induced Phosphatase I Deficiency Exacerbates Myocardial Infarction-induced Ischemic Injury  

作　　者：Ke-Mei Liu Hai-Hong Zhang Ya-Nan Wang Lian-Mei Wang Hong-Yu Chen Cai-Feng Long Lian-Feng Zhang Hong-Bing Zhang Hong-Bing Yan 

机构地区：[1]Department of Coronary Artery Disease, 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, China [2]Department of Physiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China [3]Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100029, China [4]Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China

出　　处：《Chinese Medical Journal》2017年第11期1333-1341,共9页中华医学杂志（英文版）

摘　　要：Background： Myocardial infarction （MI） is a major disease burden. Wild-type p53-induced phosphatase 1 （Wipl） has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods： The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout （Wipl-KO） mice and wild-type （WT） mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight （HW/BW） ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending （LAD） coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin （H＆E） staining was used to determine the infarct size. Gene expression of interleukin-6 （IL-6）, turnor necrosis factor-α （TNF-α）, and interleukin-1β （IL-1β） was assessed by quantitative real-time polymerase chain reaction （qPCR）, and the levels of signal transducers and activators of transcription 3 （stat3） and phosphor-stat3 （p-stat3） were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance （ANOVA） were used for statistical analyses. Results： Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality （57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05）, increased cardiac hypertrophy （HW/BW ratio： 7 days： 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area： 7 days： 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05）, and reduced cardiac function （ejectionBackground： Myocardial infarction （MI） is a major disease burden. Wild-type p53-induced phosphatase 1 （Wipl） has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods： The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout （Wipl-KO） mice and wild-type （WT） mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight （HW/BW） ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending （LAD） coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin （H＆E） staining was used to determine the infarct size. Gene expression of interleukin-6 （IL-6）, turnor necrosis factor-α （TNF-α）, and interleukin-1β （IL-1β） was assessed by quantitative real-time polymerase chain reaction （qPCR）, and the levels of signal transducers and activators of transcription 3 （stat3） and phosphor-stat3 （p-stat3） were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance （ANOVA） were used for statistical analyses. Results： Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality （57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05）, increased cardiac hypertrophy （HW/BW ratio： 7 days： 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area： 7 days： 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05）, and reduced cardiac function （ejection

关 键 词：lschemic Injury Myocardial Infarction Wild-type p53-induced Phosphatase 1 

分 类 号：R542.22[医药卫生—心血管疾病]