Rescuing Impaired Re-endothelialization of Drug-Eluting Stents Using the Hepatocyte Growth Factor

Background: Current commercially available drug-eluting stents (DESs) are criticized for the problem of stent thrombosis by induced impaired re-endothelialization (RE). The solving of this challenge could be boosted by endothelial progenitor cells (EPCs). The purpose of this study was to examine the effects of hepatocyte growth factor (HGF) on this process. Methods: The abundance and functional capacity of circulating EPC was analyzed by a fluorescence-activated cell sorter and western blot. The in vivo effect of HGF on DES patency, RE, and neointimal formation was investigated in a hypercholesterolemic rabbit model. Results: After 7 days of HGF administration, the number of CD34+/CD133+ progenitor cells had increased significantly. HGF also significantly inhibited the onset of senescence of EPC due to a decrease in protein expression of p53 and p21. In the in vivo study, HGF-treated DES had a higher patency rate than the control group (11/12 vs. 6/12, P = 0.032). Moreover, the HGF-treated group exhibited better RE (control group: 69.5 +/- 12.9%, HGF group: 88.8 +/- 8.4%, P = 0.006), but significantly smaller areas of neointima (control group: 0.68 +/- 0.15 mm(2), HGF group: 0.45 +/- 0.18 mm(2), P = 0.02). Conclusion: HGF efficiently ameliorates the vascular response to stent implantation, and has an important redeeming influence on the deleterious endothelial effects of DES.