Tanshinone II A attenuates vascular remodeling through klf4 mediated smooth muscle cell phenotypic switching

• Published in: Scientific reports 2020-08, Vol.10 (1), p.13858, Article 13858
• Main Authors: Lou, Guanhua, Hu, Wangming, Wu, Ziqiang, Xu, Huan, Yao, Huan, Wang, Yang, Huang, Qinwan, Wang, Baojia, Wen, Li, Gong, Daoying, Chen, Xiongbing, Shi, Yaping, Yang, Lan, Xu, Yiming, Wang, Yong
• Format: Article
• Language: English
• Subjects: 631/154; 631/337; 692/308; 692/4017; 692/4019; Abietanes - pharmacology; Abietanes - therapeutic use; Animal models; Animals; Carotid artery; Cell differentiation; Cell Differentiation - genetics; Cell growth; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cells, Cultured; Gene Expression - drug effects; Humanities and Social Sciences; Immunofluorescence; Immunohistochemistry; KLF4 protein; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Mice; multidisciplinary; Muscle, Smooth, Vascular - growth & development; Phenotype; Phytotherapy; Platelet-derived growth factor; Platelet-derived growth factor BB; Rapamycin; Rats, Sprague-Dawley; Salvia miltiorrhiza; Science; Science (multidisciplinary); Smooth muscle; Vascular diseases; Vascular Diseases - drug therapy; Vascular Remodeling - drug effects; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-70887-1

The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.