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26 March 2020 : Animal Research  

Effects of a Matrix Metalloproteinase Inhibitor-Eluting Stent on In-Stent Restenosis

Jian-bo Song1ABCDEF, Jing Shen12CD, Jun Fan3AC, Zhe Zhang1C, Zheng-jia Yi1C, Shuo Bai1C, Xiao-lin Mu1C, Liang Xiao1A*

DOI: 10.12659/MSM.922556

Med Sci Monit 2020; 26:e922556

Abstract

BACKGROUND: The aim of this study was to compare changes in the extracellular matrix after implantation of a stent that elutes a matrix metalloproteinase (MMP) inhibitor (GM6001); and to determine the effects of the GM6001-eluting stent upon prevention of in-stent restenosis (ISR).

MATERIAL AND METHODS: We included 48 Guangxi Bama mini-pigs in this study. A GM6001-eluting stent was placed in one iliac artery and a stent that did not elute GM6001 was placed in the contralateral iliac artery. The iliac arteries were removed at 6 hours as well as 1, 7, 14, 56, 84, and 336 days after stent placement. Arteries were analyzed for morphometry, gelatinase content, different phenotypes of vascular smooth muscle cells (VSMCs), collagen content, apoptotic rate, and cell density.

RESULTS: The vascular lumen areas of the GM6001 group were significantly increased and the neointimal areas were significantly reduced compared with the control group from the 7 days to the 336 days. In the 2 groups, expression of MMP-2 and MMP-9 peaked simultaneously, but GM6001-eluting stents inhibited expression of MMP-2 and MMP-9 in the vascular media and neointima (especially around the struts) significantly. In the GM6001 group, expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2, myosin heavy chain 10 (MYH-10, marker of the proliferative phenotype of VSMCs), collagen content, percentage of apoptotic cells, and cell density were also decreased significantly compared with those in the control group.

CONCLUSIONS: Use of GM6001-eluting stents resulted in persistent and potent inhibition of intimal hyperplasia, an increase in luminal area, and no obvious thrombosis in the arteries of the mini-pigs.

Keywords: Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Muscle, Smooth, Vascular, Collagen, Coronary Restenosis, drug-eluting stents, Matrix Metalloproteinase Inhibitors, Myosin Heavy Chains, Neointima, Polylactic Acid-Polyglycolic Acid Copolymer, Swine, Swine, Miniature, Time Factors, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750