Portal de Periódicos da CAPES

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

2024; Nature Portfolio; Volume: 15; Issue: 1 Linguagem: Inglês

10.1038/s41467-024-50036-2

2041-1723

Ze-Long Liu, Yan Li, Yi‐Jun Lin, Mao‐Mao Shi, Mengxia Fu, Zhiqing Li, Da-Sheng Ning, Xiang-Ming Zeng, Xiang Liu, Qinghua Cui, Yue-Ming Peng, Xinmin Zhou, Yerong Hu, Jiasheng Liu, Yu-Jia Liu, Mian Wang, Chunxiang Zhang, Wei Kong, Zhi‐Jun Ou, Jing‐Song Ou,

MicroRNA in disease regulation

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.