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October 17, 2009
9:00 AM - 11:00 AM
Room Area E
Upregulation of miR-221 and miR-222 in Diabetic Vessel after Angioplasty
  **   Xiaojun Liu, Ph.D., Yunhui Cheng, M.D., Ph.D., Jian Yang, M.D., Ph.D., Chunxiang Zhang, M.D., Ph.D.
Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey
It is well established that diabetes increases atherosclerosis and restenosis after angioplasty via increasing vascular smooth muscle cell (VSMC) proliferation; however, the molecular mechanisms involved in these diabetic cellular events are currently unclear. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA is as important as a transcription factor in cell biology and disease because it is able to regulate the expression of its multiple target genes. We hypothesized that miRNAs may be involved in diabetic vascular disease. To test our hypothesis, we determined the expression of miR-221 and miR-222 in carotid arteries from diabetic obese Zuker rats and control non-diabetic lean Zucker rats. We found that the expression of miR-221 and miR-222 was significant upregulated in diabetic obese Zuker rats after angioplasty compared with the uninjured controls. In cultured VSMCs, miR-221 and miR-222 expression was increased by growth stimulators. Knockdown of miR-221 and miR-222 resulted in decreased VSMC proliferation in vitro . Using both gain-of-function and loss-of-function approaches, we found that p27(Kip1) and p57(Kip2) were two target genes that were involved in miR-221 and miR-222-mediated effect on VSMC growth. Finally, knockdown of miR-221 and miR-222 in rat carotid arteries suppressed VSMC proliferation in vivo and neointimal lesion formation after angioplasty. The results indicate that miR-221 and miR-222 are novel regulators for VSMC proliferation and neointimal hyperplasia in type II diabetes.

From Proceedings of the 2009 Annual Meeting of the American Society Anesthesiologists.