Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating macrophage-mediated inflammation

• Published in: Bioscience reports 2018-06, Vol.38 (3)
• Main Authors: Zhang, Zhidong, Liang, Kai, Zou, Gangqiang, Chen, Xiaosan, Shi, Shuaitao, Wang, Guoquan, Zhang, Kewei, Li, Kun, Zhai, Shuiting
• Format: Article
• Language: English
• Subjects: Angiotensin II - genetics; Animals; Antigens, CD - genetics; Antigens, Differentiation, Myelomonocytic - genetics; Aortic Aneurysm, Abdominal - drug therapy; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - pathology; Apolipoproteins E - genetics; Cell Movement - genetics; Cell Proliferation - genetics; Chemokine CCL2 - genetics; Disease Models, Animal; Gene Expression Regulation; Humans; Inflammation - drug therapy; Inflammation - genetics; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 9 - genetics; Mice; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Nitric Oxide Synthase Type II - genetics
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20171432

The aim of the present study was to identify abdominal aortic aneurysms (AAA)-associated miR-155 contributing to AAA pathology by regulating macrophage-mediated inflammation. Angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE-/-) mice and THP-1 cells model of miR-155 overexpression and deficiency were used in the experiments. The expression of miR-155 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cytokines were evaluated using enzyme-linked immunoabsorbent assay (ELISA). Western blotting was used to measure the levels of MMP-2, MMP-9, iNOS, and monocyte chemoattractant protein (MCP)-1 proteins. Immunostaining and transwell were used to determine CD68, elastic collagen, proliferation, and migration of vascular smooth muscle cells (VSMCs). The results showed that miR-155 and cytokines were up-regulated in AAA patients or ApoE-/- mice. Overexpression of miR-155 enhanced MMP-2, MMP-9, iNOS, and MCP-1 levels, and stimulated the proliferation and migration of VSMCs. Meanwhile, inhibition of miR-155 had the opposite effect. In addition, histology demonstrated accumulation of CD68 and elastic collagen-positive areas significantly decreased in miR-155 antagomir injection group. In conclusion, the results of the present study suggest that inhibiting miR-155 is crucial to prevent the development of AAA by regulating macrophage inflammation.