Abstract 146: MicroRNA-216a Promotes M1 Macrophages Polarization Through the Activation of Telomerase

Background: Macrophages display significant phenotypic heterogeneity and plasticity. Two subtypes exist in atherosclerotic plaques: M1 pro-inflammatory subtype and M2 anti-inflammatory subtype, which can be converted to each other under certain conditions and therefore contribute to the plaque progression. But the underlying mechanisms remain unclear. Our previous work showed that m iR-216a mediates the activation of telomerase in macrophages differentiation via the Smad3/NF-κB pathway in vitro . In the present study, we aimed to examine the role of miR-216a in macrophages polarization and atherosclerosis in vivo . Methods and Results: We applied a tandem stenosis to the right carotid artery of apolipoprotein E-deficient mice model according to doctor Chen’s method (Circ Res. 2013;113(3):252-65.), with local infiltration of the miR-216a lentivirus. At 4 weeks postoperatively, the significant effect of miR-216a on plaque area was not observed; however, the results showed that miR-216a in the carotid atherosclerotic plaques markedly increased the numbers of M1 subtype by 1.8-fold whereas simultaneously decreased M2 subtype by 2.1-fold by applying CD16/32 and Arg1 immuno-fluorescent staining. In addition, we found that miR-216a significantly reduced the amounts of collagen III by Sirius-Red staining and downregulated the mRNA expression of collagen type III alpha 1 chain (COL3A1) by 70%. Furthermore, the THP-1 macrophages were used to explore the mechanism of miR-216a on macrophages polarization, and the results showed that miR-216a and telomerase reverse transcriptase (TERT) expression were only increased in M1 macrophages. Next, TERT lentivirus and siRNA were transfected, and the results showed that TERT overexpression promoted M1 polarization; on the contrary, silencing TERT inhibited M1 polarization and suppressed M2 to M1 conversion. Conclusions: Our data indicated that miR-216a promotes M1 macrophages polarization through the activation of telomerase and reduces collagen III in mice carotid lesions, and ultimately accelerates the development of atherosclerosis.