Frontiers in Cardiovascular Medicine (Aug 2022)
Ablation of cardiomyocyte-derived BDNF during development causes myocardial degeneration and heart failure in the adult mouse heart
- Lilin Li,
- Lilin Li,
- Lilin Li,
- Lilin Li,
- Hongyan Guo,
- Hongyan Guo,
- Hongyan Guo,
- Hongyan Guo,
- Hongyan Guo,
- Binglin Lai,
- Binglin Lai,
- Binglin Lai,
- Binglin Lai,
- Chunbao Liang,
- Chunbao Liang,
- Chunbao Liang,
- Chunbao Liang,
- Hongyi Chen,
- Hongyi Chen,
- Hongyi Chen,
- Hongyi Chen,
- Yilin Chen,
- Yilin Chen,
- Yilin Chen,
- Yilin Chen,
- Weimin Guo,
- Weimin Guo,
- Weimin Guo,
- Weimin Guo,
- Ziqiang Yuan,
- Ruijin Huang,
- Ruijin Huang,
- Zhaohua Zeng,
- Liying Liang,
- Hui Zhao,
- Xin Zheng,
- Xin Zheng,
- Xin Zheng,
- Xin Zheng,
- Yanmei Li,
- Yanmei Li,
- Yanmei Li,
- Yanmei Li,
- Qin Pu,
- Xufeng Qi,
- Xufeng Qi,
- Xufeng Qi,
- Xufeng Qi,
- Dongqing Cai,
- Dongqing Cai,
- Dongqing Cai,
- Dongqing Cai
Affiliations
- Lilin Li
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Lilin Li
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Lilin Li
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Lilin Li
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Hongyan Guo
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Hongyan Guo
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Hongyan Guo
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Hongyan Guo
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Hongyan Guo
- Jiangxi Provincial Key Laboratory of Medical Immunology and Immunotherapy, Jiangxi Academy of Medical Sciences, Nanchang, China
- Binglin Lai
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Binglin Lai
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Binglin Lai
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Binglin Lai
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Chunbao Liang
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Chunbao Liang
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Chunbao Liang
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Chunbao Liang
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Hongyi Chen
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Hongyi Chen
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Hongyi Chen
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Hongyi Chen
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Yilin Chen
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Yilin Chen
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Yilin Chen
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Yilin Chen
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Weimin Guo
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Weimin Guo
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Weimin Guo
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Weimin Guo
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Ziqiang Yuan
- Department of Medical Oncology, Robert Wood Johnson of Medical School, Cancer Institute of New Jersey, New Brunswick, NJ, United States
- Ruijin Huang
- Department of Neuroanatomy, Institute of Anatomy, University of Bonn, Bonn, Germany
- Ruijin Huang
- Department of Anatomy and Molecular Embryology, Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany
- Zhaohua Zeng
- Division of Cardiology, Department of Internal Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Liying Liang
- Division of Cardiology, Department of Internal Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Hui Zhao
- 0Stem Cell and Regeneration TRP, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
- Xin Zheng
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Xin Zheng
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Xin Zheng
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Xin Zheng
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Yanmei Li
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Yanmei Li
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Yanmei Li
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Yanmei Li
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Qin Pu
- Department of Neuroanatomy, Institute of Anatomy, University of Bonn, Bonn, Germany
- Xufeng Qi
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Xufeng Qi
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Xufeng Qi
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Xufeng Qi
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- Dongqing Cai
- Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China
- Dongqing Cai
- Joint Laboratory for Regenerative Medicine, Chinese University of Hong Kong-Jinan University, Guangzhou, China
- Dongqing Cai
- International Base of Collaboration for Science and Technology (JNU), The Ministry of Science and Technology and Guangdong Province, Guangzhou, China
- Dongqing Cai
- Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, China
- DOI
- https://doi.org/10.3389/fcvm.2022.967463
- Journal volume & issue
-
Vol. 9
Abstract
ObjectiveBrain-derived neurotrophic factor (BDNF) and its receptor TrkB-T1 were recently found to be expressed in cardiomyocytes. However, the functional role of cardiomyocyte-derived BDNF in heart pathophysiology is not yet fully known. Recent studies revealed that BDNF-TrkB pathway plays a critical role to maintain integrity of cardiac structure and function, cardiac pathology and regeneration of myocardial infarction (MI). Therefore, the BDNF-TrkB pathway may be a novel target for myocardial pathophysiology in the adult heart.Approach and resultsIn the present study, we established a cardiomyocyte-derived BDNF conditional knockout mouse in which BDNF expression in developing cardiomyocytes is ablated under the control of the Myosin heavy chain 6 (MYH6) promoter. The results of the present study show that ablation of cardiomyocyte-derived BDNF during development does not impair survival, growth or reproduction; however, in the young adult heart, it causes cardiomyocyte death, degeneration of the myocardium, cardiomyocyte hypertrophy, left atrial appendage thrombosis, decreased cardiac function, increased cardiac inflammation and ROS activity, and metabolic disorders, leading to heart failure (HF) in the adult heart and eventually resulting in a decrease in the one-year survival rate. In addition, ablation of cardiomyocyte-derived BDNF during the developmental stage leads to exacerbation of cardiac dysfunction and poor regeneration after MI in adult hearts.ConclusionCardiomyocyte-derived BDNF is irreplaceable for maintaining the integrity of cardiac structure and function in the adult heart and regeneration after MI. Therefore, the BDNF-TrkB pathway will be a novel target for myocardial pathophysiology in the adult heart.
Keywords
- cardiomyocyte
- cardiomyocyte-derived BDNF conditional knockout
- heart failure
- degeneration of the myocardium
- myocardial infarction
