2. Academic Validation
  3. Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA 4-Dependent CCN 1 Secretion

Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA 4-Dependent CCN 1 Secretion

  • J Am Heart Assoc. 2018 Sep 18;7(18):e009111. doi: 10.1161/JAHA.118.009111.
Sumei Cui 1 2 3 4 5,  Li Xue 1 2 3 4 5,  Feihong Yang 1 2 3 4 5,  Shuai Dai 1 2 3 4 5,  Ziqi Han 1 2 3 4 5,  Kai Liu 6,  Baoshan Liu 1 2 3 4 5,  Qiuhuan Yuan 1 2 3 4 5,  Zhaoqiang Cui 7,  Yun Zhang 5,  Feng Xu 1 2 3 4 5,  Yuguo Chen 1 2 3 4 5
Affiliations

Affiliations

  • 1 1 Department of Emergency Qilu Hospital Shandong University Jinan China.
  • 2 2 Chest Pain Center Qilu Hospital Shandong University Jinan China.
  • 3 3 Institute of Emergency and Critical Care Medicine Shandong University Jinan China.
  • 4 4 Key Laboratory of Emergency and Critical Care Medicine of Shandong Province Qilu Hospital Shandong University Jinan China.
  • 5 5 Key Laboratory of Cardiovascular Remodeling & Function Research Chinese Ministry of Education & Chinese Ministry of Public Health Qilu Hospital Shandong University Jinan China.
  • 6 6 Cardiovascular Surgery Department Qilu Hospital Shandong University Jinan China.
  • 7 7 Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai China.
PMID: 30371213 DOI: 10.1161/JAHA.118.009111
Abstract

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 -β-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 ( CCN 1), interleukin-1α, tumor necrosis factor α, and monocyte chemoattractant protein-1. In vivo, a tail vein injection of AAV 9- Gata4-sh RNA significantly attenuated senescence-related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence-related secretory phenotype factors, CCN 1 administration reduced myofibroblast viability in vitro and rescued the deleterious effect of AAV 9- Gata4-sh RNA in vivo. Conclusions Myocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA-binding factor 4- CCN 1 pathway.

Keywords

CCN1; fibrosis; myocardial ischemia; senescence.

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