Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA4-Dependent CCN1 Secretion

被引:55
作者
Cui, Sumei [1 ,2 ,3 ,4 ,6 ,7 ]
Xue, Li [1 ,2 ,3 ,4 ,6 ,7 ]
Yang, Feihong [1 ,2 ,3 ,4 ,6 ,7 ]
Dai, Shuai [1 ,2 ,3 ,4 ,6 ,7 ]
Han, Ziqi [1 ,2 ,3 ,4 ,6 ,7 ]
Liu, Kai [5 ]
Liu, Baoshan [1 ,2 ,3 ,4 ,6 ,7 ]
Yuan, Qiuhuan [1 ,2 ,3 ,4 ,6 ,7 ]
Cui, Zhaoqiang [3 ,4 ,8 ]
Zhang, Yun [3 ,4 ]
Xu, Feng [1 ,2 ,3 ,4 ,6 ,7 ]
Chen, Yuguo [1 ,2 ,3 ,4 ,6 ,7 ]
机构
[1] Shandong Univ, Dept Emergency, Jinan, Shandong, Peoples R China
[2] Shandong Univ, Key Lab Emergency & Crit Care Med Shandong Prov, Jinan, Shandong, Peoples R China
[3] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Jinan, Shandong, Peoples R China
[4] Shandong Univ, Chinese Minist Publ Hlth, Jinan, Shandong, Peoples R China
[5] Shandong Univ, Cardiovasc Surg Dept, Jinan, Shandong, Peoples R China
[6] Shandong Univ, Qilu Hosp, Jinan, Shandong, Peoples R China
[7] Shandong Univ, Inst Emergency & Crit Care Med, Jinan, Shandong, Peoples R China
[8] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai, Peoples R China
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2018年 / 7卷 / 18期
基金
中国国家自然科学基金;
关键词
CCN1; fibrosis; myocardial ischemia; senescence; MATRICELLULAR PROTEIN CCN1; ACUTE MYOCARDIAL-INFARCTION; ALDEHYDE DEHYDROGENASE 2; CELLULAR SENESCENCE; INDUCTION; FAILURE; FIBROSIS; YOUNGER; CELLS; ALDH2;
D O I
10.1161/JAHA.118.009111
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Stress-induced cell premature senescence participates in a variety of tissue and organ remodeling by secreting such proteins as proinflammatory cytokines, chemokines, and growth factors. However, the role of cardiomyocyte senescence in heart remodeling after acute myocardial infarction has not been thoroughly elucidated to date. Therefore, we sought to clarify the impact of premature myocardial senescence on postinfarction heart function. Methods and Results-Senescence markers, including p16(INK4a), p21(CIP1/WAF1), and SA-beta-gal staining, were analyzed in several heart disease models by immunostaining. Both postinfarction mouse hearts and ischemic human myocardium demonstrated increased senescence markers. Additionally, senescence-related secretory phenotype was activated after acute myocardial infarction, which upregulated senescence-related secretory phenotype factors, including CCN family member 1 (CCN1), interleukin-1 alpha, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In vivo, a tail vein injection of AAV9-Gata4-shRNA significantly attenuated senescence-related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence-related secretory phenotype factors, CCN1 administration reduced myofibroblast viability in vitro and rescued the deleterious effect of AAV9-Gata4-shRNA in vivo. Conclusions-Myocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA-binding factor 4-CCN1 pathway.
引用
收藏
页数:17
相关论文
共 30 条
[1]  
Committee for the Update of the Guide for the Care and Use of Laboratory Animals, 2011, GUIDE CARE USE LAB A
[2]   β-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction [J].
Dondo, Tatendashe B. ;
Hall, Marlous ;
West, Robert M. ;
Jernberg, Tomas ;
Lindahl, Bertil ;
Bueno, Hector ;
Danchin, Nicolas ;
Deanfield, John E. ;
Hemingway, Harry ;
Fox, Keith A. A. ;
Timmis, Adam D. ;
Gale, Chris P. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2017, 69 (22) :2710-2720
[3]  
Fountoulaki Katerina, 2015, Card Fail Rev, V1, P64, DOI 10.15420/cfr.2015.1.2.64
[4]   Matrix Protein CCN1 Is Critical for Prostate Carcinoma Cell Proliferation and TRAIL-Induced Apoptosis [J].
Franzen, Carrie A. ;
Chen, Chih-Chiun ;
Todorovic, Viktor ;
Juric, Vladislava ;
Monzon, Ricardo I. ;
Lau, Lester F. .
MOLECULAR CANCER RESEARCH, 2009, 7 (07) :1045-1055
[5]   A Novel and Efficient Model of Coronary Artery Ligation and Myocardial Infarction in the Mouse [J].
Gao, Erhe ;
Lei, Yong Hong ;
Shang, Xiying ;
Huang, Z. Maggie ;
Zuo, Lin ;
Boucher, Matthieu ;
Fan, Qian ;
Chuprun, J. Kurt ;
Ma, Xin L. ;
Koch, Walter J. .
CIRCULATION RESEARCH, 2010, 107 (12) :1445-+
[6]   An Update on Cardioprotection A Review of the Latest Adjunctive Therapies to Limit Myocardial Infarction Size in Clinical Trials [J].
Gerczuk, Paul Z. ;
Kloner, Robert A. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2012, 59 (11) :969-978
[7]   SERIAL CULTIVATION OF HUMAN DIPLOID CELL STRAINS [J].
HAYFLICK, L ;
MOORHEAD, PS .
EXPERIMENTAL CELL RESEARCH, 1961, 25 (03) :585-+
[8]   The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing [J].
Jun, Joon-Il ;
Lau, Lester F. .
NATURE CELL BIOLOGY, 2010, 12 (07) :676-U106
[9]   The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4 [J].
Kang, Chanhee ;
Xu, Qikai ;
Martin, Timothy D. ;
Li, Mamie Z. ;
Demaria, Marco ;
Aron, Liviu ;
Lu, Tao ;
Yankner, Bruce A. ;
Campisi, Judith ;
Elledge, Stephen J. .
SCIENCE, 2015, 349 (6255)
[10]   Matricellular Protein CCN1 Promotes Regression of Liver Fibrosis through Induction of Cellular Senescence in Hepatic Myofibroblasts [J].
Kim, Ki-Hyun ;
Chen, Chih-Chiun ;
Monzon, Ricardo I. ;
Lau, Lester F. .
MOLECULAR AND CELLULAR BIOLOGY, 2013, 33 (10) :2078-2090