The Role of VEGF in Intervention-Mediated Injuries: Neointimal Hyperplasia and In-Stent Restenosis

Background: The role of vascular endothelial growth factor (VEGF) in intimal hyperplasia has been investigated and discussed numerous times in the literature, producing contrary results and controversial outcomes. In particular, research concerned with the effects of VEGF after catheter-mediated injuries regarding the development of neointimal hyperplasia resulted in diverging conclusions. Methods: A systematic review based on PRISMA principles using MEDLINE was conducted. In summary, 66 publications met the qualifying criteria to be included in this review. Results: VEGF can both cause and attenuate neointimal hyperplasia depending on its site of application and production. Endogenous VEGF produced in the media and adventitia promotes intimal hyperplasia after vascular injury, while exogenous VEGF delivered through drug eluting-stents or by gene therapy can ameliorate re-endothelialization and thereby inhibit intima hyperplasia. Conclusions: The understanding of post-injury released cytokines such as VEGF holds great promise for currently used therapeutic applications and potential for applications to be investigated in the future.