BDNF-mediated migration of cardiac microvascular endothelial cells is impaired during ageing

J Cell Mol Med. 2012 Dec;16(12):3105-15. doi: 10.1111/j.1582-4934.2012.01621.x.

Abstract

This study indicates that brain-derived neurotrophic factor (BDNF) can promote young cardiac microvascular endothelial cells (CMECs) to migrate via the activation of the BDNF-TrkB-FL-PI3K/Akt pathway, which may benefit angiogenesis after myocardial infarction (MI). However, the ageing of CMECs led to changes in the expression of receptor Trk isoforms in that among the three isoforms (TrkB-FL, TrkB-T1 and TrkB-T2), only one of its truncated isoforms, TrkB-T1, continued to be expressed, which leads to the dysfunction of its ligand, a decrease in the migration of CMECs and increased injury in ageing hearts. This shift in receptor isoforms in aged CMECs, together with changes in the ageing microenvironment, might predispose ageing hearts to decreased angiogenic potential and increased cardiac pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Movement*
  • Endothelial Cells / physiology*
  • Female
  • Heart
  • Myocardial Infarction
  • Neovascularization, Physiologic / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / metabolism*
  • Signal Transduction

Substances

  • Brain-Derived Neurotrophic Factor
  • Protein Isoforms
  • Phosphatidylinositol 3-Kinases
  • Receptor, trkB
  • Proto-Oncogene Proteins c-akt