EphrinB2/EphB4 pathway in postnatal angiogenesis: a potential therapeutic target for ischemic cardiovascular disease

Angiogenesis. 2016 Jul;19(3):297-309. doi: 10.1007/s10456-016-9514-9. Epub 2016 May 23.

Abstract

Ischemic cardiovascular disease remains one of the leading causes of morbidity and mortality in the world. Proangiogenic therapy appears to be a promising and feasible strategy for the patients with ischemic cardiovascular disease, but the results of preclinical and clinical trials are limited due to the complicated mechanisms of angiogenesis. Facilitating the formation of functional vessels is important in rescuing the ischemic cardiomyocytes. EphrinB2/EphB4, a novel pathway in angiogenesis, plays a critical role in both microvascular growth and neovascular maturation. Hence, investigating the mechanisms of EphrinB2/EphB4 pathway in angiogenesis may contribute to the development of novel therapeutics for ischemic cardiovascular disease. Previous reviews mainly focused on the role of EphrinB2/EphB4 pathway in embryo vascular development, but their role in postnatal angiogenesis in ischemic heart disease has not been fully illustrated. Here, we summarized the current knowledge of EphrinB2/EphB4 in angiogenesis and their interaction with other angiogenic pathways in ischemic cardiovascular disease.

Keywords: Angiogenesis; EphrinB2/EphB4 pathway; Ischemic cardiovascular disease; VEGF-Dll4/Notch-EphrinB2 cascade; Vessel maturation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ephrin-B2 / chemistry
  • Ephrin-B2 / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Ligands
  • Membrane Proteins / physiology
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / physiopathology*
  • Neovascularization, Physiologic* / drug effects
  • Receptor, EphB4 / chemistry
  • Receptor, EphB4 / physiology*
  • Receptors, Notch / physiology
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Ephrin-B2
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Receptors, Notch
  • Vascular Endothelial Growth Factor A
  • delta protein
  • Receptor, EphB4