Study of preventing venous graft restenosis by local application of simvastatin and mechanical preconditioning
- VernacularTitle:局部应用辛伐他汀和机械预处理方法预防静脉移植物再狭窄的研究
- Author:
Chenyu ZHAO
1
;
Yuwei PAN
2
;
Liujun JIA
3
;
Yan ZHANG
1
;
Yabing DUAN
1
;
Li DING
1
;
Hansong SUN
1
Author Information
1. Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100039, P. R. China
2. Department of Biochemistry and Molecular Biology, College of Biology, China Agricultural University, Beijing, 100094, P. R. China
3. Animal Laboratory Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 102300, P. R. China
- Publication Type:Journal Article
- Keywords:
Local application;
simvastatin;
mechanical preconditioning;
vein graft restenosis;
coronary artery bypass grafting
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2023;30(02):291-298
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of simvastatin and mechanical pretreatment on intimal hyperplasia of venous graft and its mechanism. Methods Twelve New Zealand rabbits were selected and randomly divided into 4 groups: a blank control group, a simvastatin topical treatment group, a mechanical precondition group and a combined group (n=3 in each group). Ultrasound was used to evaluate the changes of graft wall and blood flow velocity in the graft, and pathological section was used to evaluate the intimal hyperplasia. Human umbilical cord endodermal cells were cultured in vitro. A simvastatin group and a solvent control group were set to detect YAP phosphorylation, downstream target gene expression and cell proliferation. Results Vascular ultrasound showed that except the simvastatin topical treatment group, the flow velocity in vein grafts in the other three groups significantly increased 21 days after surgery compared with 7 days after surgery (P<0.01). Pathological sections showed that the thickness of new intima in the simvastatin topical treatment group, mechanical precondition group, combined group and blank control group were 45.56±4.11 μm, 201.28±16.71 μm, 143.57±7.82 μm, 249.45±13.33 μm, respectively, and there were statistical differences compared with the blank control group (P<0.05). In vitro results showed that compared with the solvent control group, cell death was observed in high concentration simvastatin (5 mmol/L) group, cell proliferation was inhibited in low concentration simvastatin (2.5 mmol/L) group (P<0.05), the expression of YAP protein in the simvastatin group was unchanged, but the expression of phosphorylated YAP protein significantly increased (P<0.05), and the expression of downstream target gene ccn1 was down-regulated (P<0.001). Conclusion Intravascular local application of simvastatin and mechanical preconditioning alone or in combination can inhibit intimal hyperplasia of venous graft. High concentration of simvastatin has cytotoxicity, while low concentration of simvastatin has inhibitory effect on cell proliferation. Simvastatin can inhibit the formation of new intima by inhibiting the entry of YAP into the nucleus and reducing the transcription of cell proliferation-related target gene ccn1.
