Related Experiment Video
Updated: Jun 21, 2025
Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions
Published on: March 8, 2019
Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice
Ze-Long Liu1,2,3,4,5, Yan Li1,2,3,4,5, Yi-Jun Lin1,2,3,4,5
1Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
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.
Insights
Aging worsens aortic aneurysm and dissection (AAD) through a miR-1204 and myosin light chain kinase (MYLK) pathway. This microRNA promotes vascular smooth muscle cell senescence, contributing to AAD development.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Molecular Medicine
Background:
- The mechanisms linking aging to aortic aneurysm and dissection (AAD) are not fully understood.
- MicroRNAs (miRNAs) are implicated in various cardiovascular diseases, but their specific role in age-related AAD requires further elucidation.
Purpose of the Study:
- To investigate the role of microRNAs in the pathogenesis of age-related aortic aneurysm and dissection (AAD).
- To identify specific molecular pathways involved in the exacerbation of AAD by aging.
Main Methods:
- Screening of differentially expressed plasma microRNAs (miRNAs) in participants with and without AAD.
- Investigating the regulatory role of miR-1204 in vascular smooth muscle cell (VSMC) senescence and phenotype.
- Utilizing mouse models to assess the impact of miR-1204 inhibition and MYLK overexpression on AAD development.
Main Results:
- miR-1204 was found to be significantly increased in plasma and aorta of elder patients with AAD, correlating positively with age.
- miR-1204 promotes VSMC senescence and a senescence-associated secretory phenotype (SASP) via targeting MYLK, creating a positive feedback loop.
- Inhibition of miR-1204 attenuated AAD development in mouse models, while MYLK overexpression reversed miR-1204-induced detrimental effects on VSMCs.
Conclusions:
- Aging exacerbates AAD through the miR-1204-MYLK signaling axis.
- miR-1204 plays a critical role in inducing VSMC senescence and phenotypic changes, contributing to AAD pathogenesis.
- Targeting the miR-1204-MYLK pathway presents a potential therapeutic strategy for age-related AAD.
