Therapeutic strategies to combat neointimal hyperplasia in vascular grafts

Abstract

Neointimal hyperplasia (NIH) in bypass conduits such as veins and prosthetic grafts is an important clinical entity that limits the long-term success of vascular interventions. Although the development of NIH in the conduits shares many of the same features of NIH that develops in native arteries after injury, vascular grafts are exposed to unique circumstances that predispose them to NIH, including surgical trauma related to vein handling, hemodynamic changes creating areas of low flow, and differences in biocompatibility between the conduit and the host environment. Multiple different approaches, including novel surgical techniques and targeted gene therapies, have been developed to target and prevent the causes of NIH. Recently, the PREVENT trials, the first molecular biology trials in vascular surgery aimed at preventing NIH, have failed to produce improved clinical outcomes, highlighting the incomplete knowledge of the pathways leading to NIH in vascular grafts. In this review, we aim to summarize the pathophysiologic pathways that underlie the formation of NIH in both vein and synthetic grafts and discuss current and potential mechanical and molecular approaches under investigation that may limit NIH in vascular grafts.

Keywords::

• edifoligide
• fistula
• gene therapy
• heparin
• neointimal hyperplasia
• patch
• vascular graft
• vein

Acknowledgements

The authors appreciate the help of Drs Akimasa Yamashita and Fabio Kudo in creating and staining the specimens in Figures 2 and 4.

Financial & competing interests disclosure

This work was supported by NIH grant R01-HL095498, the American Vascular Association William J von Liebig Award, and the resources and the use of facilities at the VA Connecticut Healthcare System, West Haven, CT, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.