Overexpression of microRNA-30a contributes to the development of aortic dissection by targeting lysyl oxidase.

OBJECTIVE:To explore the role of microRNA (miR)-30a in the development of aortic dissection. METHODS:Human aortic specimens of aortic dissections and aneurysms were harvested. Aortic specimens from donors for heart transplantation served as controls. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with agomiR-30a or antagomiR-30a, and control cells were incubated with empty vectors. Rats were pretreated with agomiR-30a or antagomiR-30a (5 × 10⁷ transfection units every 3 days for 4 weeks), and empty vectors were infused to controls. Acute aortic dissection was induced by subcutaneous infusion of angiotensin II (1 μg · kg^-1 · min^-1 for 24 hours). Protein expressions of lysyl oxidase (LOX) and elastin and gene expression of miR-30a were measured in VSMCs and human and rat aortic specimens by Western blot analysis and quantitative real-time polymerase chain reaction. RESULTS:Gene expression of miR-30a was much higher, and protein abundance of LOX and elastin was significantly lower, in the aortic dissection specimens (P < .05 vs controls). Transfection of agomiR-30a markedly decreased the luciferase activity of LOX in VSMCs of wild type, but not of LOX 3'-UTR mutant (P = .002). In cultured VSMCs, transfection of agomiR-30a dramatically enhanced the gene expression of miR-30a and down-regulated the protein abundance of LOX and elastin (P < .05 vs controls). Pretreatment with agomiR-30a in vivo enhanced miR-30a expression and down-regulated the protein abundance of LOX and elastin in rat aortas (P < .05 vs controls). The rate of dissection was significantly higher in rats pretreated with agomiR-30a (P = .003 vs controls). CONCLUSIONS:Overexpression of miR-30a contributes to the development of aortic dissection, possibly by targeting LOX. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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