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

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/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. Conclusion: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.

Detection of Type I and III collagen in porcine acellular matrix using HPLC–MS

“…In addition, the collagen type and ratio in tissue were certain, so the change of the ratio might indicate the occurrence of some diseases, such as pulmonary fibrosis, arteriosclerosis and aneurysm, etc. The HPLC−MS method could be used to investigate the relationship between diseases and collagen change [ 38–40 ]. The degradation of implanted-collagen in vivo was usually detected by the radioactive labeling or Sirius red method, etc.…”

Sacubitril/valsartan inhibits the proliferation of vascular smooth muscle cells through notch signaling and ERK1/2 pathway

“…MMP-9 belongs to the matrix metalloproteinase family, which can degrade the vascular basement membrane and extracellular matrix [ 39 ], and is an important marker in the process of cell migration. The study found that overexpression of MMP-9 can promote the migration of VSMCs to the intima and reduce the content of intima matrix [ 40 ]. Therefore, the results of this experiment indicate that valsartan/sacubitril can inhibit the proliferation and migration of VSMCs induced by AngII.…”

Preventive Effect and Mechanism of Crossostephium chinense Extract on Balloon Angioplasty-Induced Neointimal Hyperplasia

“…The partial inhibitory mechanisms underlying the prevention of neointimal formation may be attributed to the gelatinase deficiency-caused reduction in the invasion, migration, and proliferation of VSMCs [ 36 , 37 ]. In addition, the use of a drug-eluting stent coated with a broad-spectrum MMP inhibitor (GM6001) could prevent the development of restenosis [ 38 ]. The aforementioned findings imply that suppressing MMP expression or activity can be an effective strategy for preventing neointimal formation.…”