Abstract 320: MicroRNA-133a Attenuates the Development of Thoracic Aortic Aneurysm

• DOI: 10.1161/res.125.suppl_1.320
• Publication Date: 2019-10-16T17:53:59Z
• Authors: Adam W Akerman; Elizabeth N Collins; Jessica K Harrison; Joyce Oh; Lauren B Collins; Jessica Riopedre; Amari DeVaughn; Charles M Raybuck; John S Ikonomidis
• Keywords: Desmin; Myofibroblast; Phenotypic switching

Rationale: Thoracic aortic aneurysms (TAA) result from dysregulated remodeling of the vascular extracellular matrix, and may occur as altered resident cellular phenotype. MicroRNA-133a is reduced in clinical TAA specimens plays an inhibitory role regulation pathological phenotypic switch cells. Accordingly, this study tested hypothesis that miR-133a replacement attenuates development TAA. Methods Results: was induced wild type mice (0.5M CaCl 2 application, 15 minutes). Following 4 weeks, diameter increased compared to sham operated controls (1094 ± 38 vs 654 8 μm; p<0.05, n=7). Copy number miR-133a, quantitated by ddPCR, tissue (0.28 0.04 0.68 0.11 copy per U6; p<0.05 control, While no change smooth muscle cell specific Desmin nor α-smooth actin were detected, increase fibroblast discoidin domain receptor (DDR2) myosin heavy chain 11 (MYH11) observed tissue. Combined, these results are consistent with emergence a population myofibroblasts development. fibroblasts isolated control tissues (n=10). (0.41 0.14 1.60 0.43 p < 0.05 control). phenotype controls; adhesion (-0.85±0.02 -0.77±0.02), migration (63±4% 47±4%), rate collagen disk contraction over 7 hours (-12.2±1.6 -8.5±1.0) (all values, Finally, after induction mice, single tail vein injection either overexpression or scrambled sequence (control) lentivirus performed. attenuated (800 18 μm 1016 16 control; n=8). Conclusion: Aortic during progression, murine model. These unique findings suggest stable alterations be associated matrix remodeling, lead novel therapeutic strategy.