Thymidine phosphorylase: A potential new target for treating cardiovascular disease

Trends Cardiovasc Med. 2018 Apr;28(3):157-171. doi: 10.1016/j.tcm.2017.10.003. Epub 2017 Oct 20.

Abstract

We recently found that thymidine phosphorylase (TYMP), also known as platelet-derived endothelial cell growth factor, plays an important role in platelet activation in vitro and thrombosis in vivo by participating in multiple signaling pathways. Platelets are a major source of TYMP. Since platelet-mediated clot formation is a key event in several fatal diseases, such as myocardial infarction, stroke and pulmonary embolism, understanding TYMP in depth may lead to uncovering novel mechanisms in the development of cardiovascular diseases. Targeting TYMP may become a novel therapeutic for cardiovascular disorders. In this review article, we summarize the discovery of TYMP and the potential molecular mechanisms of TYMP involved in the development of various diseases, especially cardiovascular diseases. We also offer insights regarding future studies exploring the role of TYMP in the development of cardiovascular disease as well as in therapy.

Keywords: Cancer; Platelets; Thrombosis; Thymidine phosphorylase.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / genetics
  • Drug Discovery / methods*
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods*
  • Protein Conformation
  • Structure-Activity Relationship
  • Thymidine Phosphorylase / antagonists & inhibitors*
  • Thymidine Phosphorylase / chemistry
  • Thymidine Phosphorylase / genetics
  • Thymidine Phosphorylase / metabolism

Substances

  • Cardiovascular Agents
  • Enzyme Inhibitors
  • TYMP protein, human
  • Thymidine Phosphorylase