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MiR–133a regulates cardiovascular cell development. However, its impact on vascular smooth muscle cell (VSMC) growth during atherosclerosis remains unclear. Galactosyltransferase 1–associating protein (GTAP), plays a role in stem cell growth. This study will analyze the role of miR–133a in regulation VSMC growth in atherosclerosis.
Methods and Results
VSMC cultured from the aorta of wild type (WT) and ApoE–/– mice. Both of ox–LDL and anti–miR–133a exerted inhibitory effects on WT and to a less extent, ApoE–/– VSMC growth. Compared to WT VSMC, the ApoE–/– cells expressed lower levels of miR–133a and insulinlike growth factor–1 receptor (IGF–1R). Inhibition of miR–133a by anti–miR–133a decreased IGF–1R but increased GTAP (Fig.1), indicating that GTAP serves as a target of miR–133a. Western blot showed that IGF–1R was lower than those of untreated control while GTAP was increased by anti–miR–133a. IGF–1R protein degradation was inhibited when GTAP was reduced by siRNA–GTAP. Moreover, miR–133a precursor decreased GTAP while increasing IGF–1R and IGF–1–driven VSMC growth. Down–regulation of miR–133a decreases IGF–1R and slow down VSMC growth. MiR–133a failed to regulate IGF–1R when GTAP was repressed by siRNA–GTAP.
In atherosclerosis, miR–133a may serves as a positive regulator of IGF–1R and VSMC growth by targeting GTAP. Manipulation of the miR–133a/GTAP/IGF–1R pathway offers a new opportunity to control the effects of atherogenic factors on VSMC proliferation.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Cell Therapy and Angiogenesis
Abstract Category: 42. TCT@ACC–i2: Cell Therapy & Angiogenesis
Presentation Number: 2110–233
- 2013 American College of Cardiology Foundation