The Multiple Roles of Chemokines in the Mechanisms of Stent Biocompatibility

Dhanya Ravindran, Keyvan Karimi Galougahi, Joanne T M Tan, Mary M Kavurma, Christina A Bursill

Research output: Contribution to journalArticlepeer-review

Abstract

While the advent of drug-eluting stents has been clinically effective in substantially reducing the rates of major stent-related adverse events compared to bare metal stents, vascular biological problems such as neointimal hyperplasia, delayed re-endothelialisation, late stent thrombosis are not eliminated and, increasingly, neoatherosclerosis is the underlying mechanism for very late stent failure. Further understanding regarding the mechanisms underlying the biological responses to stent deployment is therefore required so that new and improved therapies can be developed. This review will discuss the accumulating evidence that the chemokines, small inflammatory proteins, play a role in each key biological process of stent biocompatibility. It will address the chemokine system in its specialised roles in regulating the multiple facets of vascular biocompatibility including neointimal hyperplasia, endothelial progenitor cell mobilisation and re-endothelialisation after vascular injury, platelet activation and thrombosis, as well as neoatherosclerosis. The evidence in this review suggests that chemokine-targeting strategies may be effective in controlling the patho-biological processes that lead to stent failure. Preclinical studies provide evidence that inhibition of specific chemokines and/or broad-spectrum inhibition of the CC-chemokine class prevents neointimal hyperplasia, reduces thrombosis and suppresses the development of neoatherosclerosis. In contrast, however, to these apparent deleterious effects of chemokines on stent biocompatibility, the CXC chemokine, CXCL12, is essential for the mobilisation and recruitment of endothelial progenitor cells that make important contributions to re-endothelialisation post-stent deployment. This suggests that future chemokine inhibition strategies would need to be correctly targeted so that all key stent biocompatibility areas could be addressed, without compromising important adaptive biological responses.

Original languageEnglish
JournalCardiovascular Research
DOIs
Publication statusE-pub ahead of print - 20 Mar 2020
Externally publishedYes

Keywords

  • drug-eluting stents
  • stent-related adverse events
  • bare metal stents
  • vascular biological problems
  • neointimal hyperplasia
  • delayed re-endothelialisation
  • late stent thrombosis
  • neoatherosclerosis
  • chemokines
  • stent biocompatibility
  • endothelial progenitor cell mobilisation
  • re-endothelialisation

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