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
  • 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. [email protected].
  • 14. Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P.R. China. [email protected].
  • 15. National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. [email protected].
  • 16. NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Guangzhou, P.R. China. [email protected].
  • 17. Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, P.R. China. [email protected].
  • 18. Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. [email protected].
  • 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. [email protected].
  • 20. Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China. [email protected].
  • 21. National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. [email protected].
  • 22. NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Guangzhou, P.R. China. [email protected].
  • 23. Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, P.R. China. [email protected].
  • 24. Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, P.R. China. [email protected].
  • 25. Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China. [email protected].
  • # 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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