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. 2018 Apr 23;137(17):1824–1841. doi: 10.1161/CIRCULATIONAHA.117.027799

Figure 7.

Figure 7.

Modulation of miR-22 expression in the injured arteries influences neointima formation. A through C, Local enforced expression of miR-22 reduces neointima formation in the injured femoral arteries. After wire-induced injury, 100 µL of 30% pluronic gel containing 2.5 nmol control AgomiR (Cel-miR-67 AgomiR) or miR-22 AgomiR per artery per mouse was immediately applied and packed around the injured femoral arteries. Three days (A) or 4 weeks (B and C) later, injured segments of femoral arteries were harvested for analyses. A, Perivascular delivery of miR-22 AgomiRs reversed the gene expression profiles in wire-induced femoral artery injury. Total RNA was harvested from uninjured and AgomiR-applied injured femoral arteries before undergoing RT-qPCR analyses. Data and error bars represent mean±SEM (n=3) (5 femoral arteries were pooled for each experiment). *P<0.05 (versus uninjured arteries). #P<0.05 (miR-22 AgomiRs versus Cel-miR-67 AgomiRs in the injured arteries). B and C, Locally enforced expression of miR-22 inhibited neointima formation in wire-injured femoral arteries. Paraffin sections from both groups (n=15 mice for Cel-miR-67 and n=13 mice for miR-22 AgomiRs) were prepared and subjected to H&E staining. Representative images (B) and morphological characteristics (C), including media area (left), intima area (middle), and intima/media (I/M) ratio (right) at 4 weeks after injury were presented. #P<0.05 (versus Cel-miR-67 AgomiRs). D through F, miR-22 inhibition promotes neointima formation in the injured arteries. After wire injury, 100 µL of 30% pluronic gel containing vehicle (mock transfection, Mock), 2.5 nmol control LNA (scrambled LNA, Scrbl-LNA), or LNA-miR-22 per artery per mouse was immediately applied and packed around injured femoral arteries. Seven days (D) or 4 weeks (E and F) later, injured segments of femoral arteries were harvested for RT-qPCR analyses (D), H&E staining (E), and morphological quantification (F) (n=5 mice for Mock and n=10 mice for LNA-miR-22 and Scrbl-LNA). Note: Dotted line (D) represents the gene expression level in the uninjured arteries, which is set as 1.0. *P<0.05 (versus uninjured arteries). #P<0.05 (LNA-miR-22 versus Mock and Scrbl-LNA). EVI1 indicates ecotropic virus integration site 1 protein homolog; HDAC4, histone deacetylase 4; H&E, hematoxylin and eosin; LNA, locked nucleic acid; MECP2, methyl-CpG binding protein 2; miR-22, microRNA-22; PCNA, proliferating cell nuclear antigen; and RT-qPCR, reverse transcription quantitative polymerase chain reaction.