miR‐29a regulates vascular neointimal hyperplasia by targeting YY1

• Published in: Cell proliferation Vol. 50; no. 3
• Main Authors: Zhang, Yu, Li, Yong Hui, Liu, Chao, Nie, Chan‐Juan, Zhang, Xin‐Hua, Zheng, Cui‐Ying, Jiang, Wen, Yin, Wei‐Na, Ren, Ming‐Hui, Jin, Yu‐Xin, Liu, Shu‐Feng, Zheng, Bin, Wen, Jin‐Kun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2017; John Wiley and Sons Inc
• Subjects: Animals; Blood vessels; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Chinese medicine; Cyclin D1; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Humans; Hyperplasia; Hyperplasia - drug therapy; Hyperplasia - genetics; Hyperplasia - pathology; Krueppel-like factor; Kruppel-Like Transcription Factors - deficiency; Kruppel-Like Transcription Factors - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Original; Rats; Rats, Sprague-Dawley; Smooth muscle; Stents; Synergistic effect; Traditional Chinese medicine; Transfection; YY1 protein; YY1 Transcription Factor - deficiency; YY1 Transcription Factor - genetics; YY1 Transcription Factor - metabolism
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12322

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.