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MiR-22 inhibits angiotensin II-induced aortic dissection and protects aortic vessel wall in mice by targeting MAPK14
Abstract
Purpose: To study the effect of miR-22 on angiotensin II-induced aortic dissection in mice, and its protective effect on aortic vessel wall, as well the involvement of MAPK-14 in these processes.
Methods: A mouse aortic dissection model was established via subcutaneous implantation of angiotensin II (1 µg/kg/min) micropump in the dorsal region. The mice (n = 30) were assigned in equal numbers to 5 groups (n = 6). All injections were given via the tail vein. The miR-22 expressions in aortas of mice in each group were determined with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot assay was used to determine the expressions of MAPK-14 protein, while H&E staining was used to measure the ratio of aortic thickness-to-diameter, and contents of collagen and elastic fibers.
Results: The expression of miR-22 in aorta of mice in miR-22 overexpression group was significantly higher than that in overexpression control group, but significantly lower in miR-22 inhibition mouse than in inhibition control mouse (p < 0.05). There was significantly lower protein expression of MAPK-14 in mice aorta in miR-22 overexpression mice than in overexpression control mice, but significantly upregulated in miR-22 inhibition mice, relative to that in inhibition control mice (p < 0.05). In the miR-22 overexpression mice, the ratio of membrane thickness-to-diameter was higher than the corresponding value in miR-22 inhibition mice. There were significantly higher contents of aortic elastic and collagen fibers in miR-22 overexpression mice than in overexpression control and miR-22 inhibition groups (p < 0.05).
Conclusion: Overexpression of miR-22 inhibits the up-regulation of expression of its target gene mapk14, increases thickness of aortic media and aortic elasticity in mice, and increase the content of collagen fibers, thereby exerting protective effect on aortic wall structure.