miR-29a regulates vascular neointimal hyperplasia by targeting YY1.

Abstract

OBJECTIVES:

The formation of vascular neointima is mainly related to impairment of the vascular endothelial barrier and abnormal proliferation and migration of smooth muscle cells. The objective of this study was to investigate whether miR-29a exerts any promoting effect on the vascular neointimal hyperplasia and if so, its mechanism.

MATERIALS AND METHODS:

RT-qPCR was performed to determine expression of miR-29a in vascular smooth muscle cells (VSMC) and vascular neointimal hyperplasia. To further understand its role, we restored its expression in VSMCs by transfection with miR-29a mimics or inhibitors. Effects of miR-29a on cell proliferation were also determined.

RESULTS:

In this study, we used two kinds of model to observe the role of miR-29a in neointimal hyperplasia induced by carotid ligation or balloon injury. The major findings were that: (i) miR-29a overexpression promoted neointimal hyperplasia induced by carotid ligation; (ii) miR-29a increased proliferation of VSMCs, one aspect of which was by targeting expression of Ying and yang 1 protein (YY1), a negative regulator of Cyclin D1. A further aspect, was by increasing expression of Krüppel-like factor 5, a positive regulator of Cyclin D1, thereby allowing formation a synergistic effect. (iii) Tongxinluo (TXL), a traditional Chinese medicine reduced neointimal formation in ligated vessels by inhibiting VSMC proliferation and migration.

CONCLUSIONS:

These findings provide a new molecular mechanism of TXL in decreasing neointima hyperplasia.

• Authors: Yu Zhang, Yong Hui Li, Chao Liu, Chan-Juan Nie, Xin-Hua Zhang, Cui-Ying Zheng, Wen Jiang, Wei-Na Yin, Ming-Hui Ren, Yu-Xin Jin, Shu-Feng Liu, Bin Zheng, Jin-Kun Wen
• Journal: Cell proliferation (Cell Prolif) Vol. 50 Issue 3 (Jun 2017) ISSN: 1365-2184 [Electronic] England
• PMID: 27910161 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Drugs, Chinese Herbal
• Klf5 protein, mouse
• Kruppel-Like Transcription Factors
• MIRN29 microRNA, mouse
• MIRN29 microRNA, rat
• MIRN29a microRNA, human
• MicroRNAs
• YY1 Transcription Factor
• tongxinluo

Topics

• Animals
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Humans
• Hyperplasia (drug therapy, genetics, pathology)
• Kruppel-Like Transcription Factors (deficiency, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• MicroRNAs (antagonists & inhibitors, genetics)
• Muscle, Smooth, Vascular (drug effects, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• YY1 Transcription Factor (deficiency, genetics, metabolism)