2. Academic Validation
  3. Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice

Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice

  • Nat Commun. 2024 Jul 16;15(1):5985. doi: 10.1038/s41467-024-50036-2.
Ze-Long Liu # 1 2 3 4 5,  Yan Li # 1 2 3 4 5,  Yi-Jun Lin # 1 2 3 4 5,  Mao-Mao Shi # 1 2 3 4 5,  Meng-Xia Fu # 1 2 3 4 5,  Zhi-Qing Li 6 7,  Da-Sheng Ning 1 2 3 4 5,  Xiang-Ming Zeng 1 2 3 4 5,  Xiang Liu 1 2 3 4 5,  Qing-Hua Cui 8,  Yue-Ming Peng 1 2 3 4 5,  Xin-Min Zhou 9,  Ye-Rong Hu 9,  Jia-Sheng Liu 1 2 3 4 5,  Yu-Jia Liu 1 2 3 4 5,  Mian Wang 2 10,  Chun-Xiang Zhang 11 12,  Wei Kong 13 14,  Zhi-Jun Ou 15 16 17 18 19,  Jing-Song Ou 20 21 22 23 24 25
Affiliations

Affiliations

  • 1 Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
  • 2 National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China.
  • 3 NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Guangzhou, P.R. China.
  • 4 Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, P.R. China.
  • 5 Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China.
  • 6 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P.R. China.
  • 7 Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P.R. China.
  • 8 Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, P.R. China.
  • 9 Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, P.R. China.
  • 10 Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
  • 11 Department of Pharmacology and Cardiovascular Research Center, Rush Medical College, Rush University Medical Center, Chicago, IL, USA.
  • 12 Department of Cardiology, Institute of Cardiovascular Research, the Affiliated Hospital, Southwest Medical University, Luzhou, China.
  • 13 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P.R. China. kongw@bjmu.edu.cn.
  • 14 Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P.R. China. kongw@bjmu.edu.cn.
  • 15 National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. Zhijunou@163.com.
  • 16 NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Guangzhou, P.R. China. Zhijunou@163.com.
  • 17 Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, P.R. China. Zhijunou@163.com.
  • 18 Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. Zhijunou@163.com.
  • 19 Division of Hypertension and Vascular Diseases, Department of Cardiology, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China. Zhijunou@163.com.
  • 20 Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China. oujs@mail.sysu.edu.cn.
  • 21 National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. oujs@mail.sysu.edu.cn.
  • 22 NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Guangzhou, P.R. China. oujs@mail.sysu.edu.cn.
  • 23 Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, P.R. China. oujs@mail.sysu.edu.cn.
  • 24 Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. oujs@mail.sysu.edu.cn.
  • 25 Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China. oujs@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 39013850 DOI: 10.1038/s41467-024-50036-2
Abstract

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma MicroRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates β-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets Myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of Transforming Growth Factor-β signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

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