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14 October 2018 : Clinical Research  

Transforming Growth Factor β1 (TGF-β1) Appears to Promote Coronary Artery Disease by Upregulating Sphingosine Kinase 1 (SPHK1) and Further Upregulating Its Downstream TIMP-1

Shoudong Wang1ADE, Qing Zhang1BC, Yingcui Wang1BD, Beian You1CDE, Qingfeng Meng1AB, Sen Zhang2BDE, Xuanlong Li2BDE, Zhiming Ge1BEF*

DOI: 10.12659/MSM.910707

Med Sci Monit 2018; 24: CLR7322-7328

Abstract

BACKGROUND: Transforming growth factor (TGF)-β1 is involved in the pathogenesis of coronary artery disease (CAD), but the mechanism of its action remains unclear. Our study aimed to investigate the role of TGF-β1 in CAD and to explore the possible mechanisms.

MATERIAL AND METHODS: A total of 60 CAD patients and 54 healthy people were included in this study. Blood samples were drawn from each participant to prepare serum. ELISA was utilized to measure serum level of TGF-β1. TGF-β1 expression vector, TGF-β1 siRNA, and TIMP-1 siRNA were transfected into human primary coronary artery endothelial cell (HCAEC) line cells, and expression of TGF-β1 sphingosine kinase 1 (SPHK1) and TIMP metallopeptidase inhibitor 1 (TIMP-1) was detected by Western blot. Cell apoptosis was detected by MTT assay.

RESULTS: Serum level of TGF-β1 was specifically higher in patients with CAD than in healthy controls. Serum levels of active TGF-β1 can be used to effectively distinguish CAD patients from healthy controls. TGF-β1 overexpression promoted the apoptosis of HCAEC and TGF-β1 siRNA silencing inhibited the apoptosis of HCAEC. TGF-β1 overexpression also promoted the expression of SPHK1 and TIMP-1. SPHK1 overexpression upregulated TIMP-1 but it showed no significant effects on TGF-β1. TIMP-1 overexpression showed no significant effects on TGF-β1 or SPHK1. SPHK1 inhibitor and TIMP-1 silencing reduced the enhancing effects of TGF-β1 overexpression on cell apoptosis.

CONCLUSIONS: TGF-β1 appears to promote CAD through the induction of cell apoptosis by upregulating SPHK1 expression and further upregulating its downstream TIMP-1.

Keywords: Coronary Disease, Gene Expression Regulation, Receptors, Transforming Growth Factor beta

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416