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

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 subjects were recruited for screening of differentially expressed plasma microRNAs. We found that miR-1204 was significantly increased in both plasma and aorta of elder patients with AAD, and was positively correlated with age. Cell senescence induced the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induced vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. miR-1204 aggravated angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuated β-aminopropionitrile monofumarate-induced AAD formation. Mechanistically, miR-1204 directly targeted myosin light chain kinase (MYLK) to promote VSMCs to acquire senescence-associated secretory phenotype (SASP) and lose their contractile phenotype. Overexpression of MYLK reversed miR-1204-induced VSMC senescence, SASP and contractile phenotype changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest aging aggravates AAD via 75 miR-1204-MYLK signaling axis. The plasma samples from young normal (< 50 years old), elder normal (> 50 years old), young patient (< 50 years old) and elder patient (> 50 years old) group (n=3 per group) were used for detecting the miRNA profiles using miRCURY LNA Array (version 19.0) (Exiqon miRCURY LNA™ microRNA Array, 7th gen-hsa, mmu and rno).