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(Circulation Research. 2008;102:e102.)
© 2008 American Heart Association, Inc.

Letters to the Editor

The Effects of Some MicroRNAs in Vascular Neointimal Formation May Depend on Cell Cycle Phase

Yunhui Cheng, Xiaojun Liu, Jian Yang, Chunxiang Zhang

RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, E-mail: zhangc3@umdnj.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

We would like to respond to the letter by Silvestri et al¹ regarding the potential role of cell cycle phase in micro (mi)RNA-mediated effects on vascular smooth muscle cells (VSMCs) and vascular neointimal formation based on our recent study.² In our study, we demonstrated that miR-21 knockdown and serum deprivation induced a disproportionate apoptosis, indicating a synergistic effect with an unclear mechanism. In addition, miR-21 knockdown had only a mild effect on the expression level of a candidate target, PTEN (phosphatase and tensin homology deleted from chromosome 10).

Recently, Vasudevan et al showed that serum deprivation with consequent arrest of the cell cycle may have profound effects on the mechanism of action of some miRNAs.^3,4 Unlike cell growth under normal conditions, miRNA may enhance mRNA translation in cells with serum deprivation and consequent growth arrest.

Based on the novel information, Silvestri et al provided us with some questions about the results and the potential explanations. First, what was the percentage of VSMCs arrested in the G₀/G₁ phase of the cell cycle by serum deprivation? If most of the cells were growth-arrested, then miR-21 may be stimulating rather than inhibiting translation of its mRNA targets. Second, heterogeneous VSMCs with the possibility of divergent actions exerted on them by miR-21, and this may explain the different results on apoptosis observed in serum-deprived VSMCs as compared with cells cultured with 10% serum. The heterogeneity of the cultured cells may also be the justification for the unpredicted small effect on . . . [Full Text of this Article]