Cardiac ischemia activates vascular endothelial cadherin promoter in both preexisting vascular cells and bone marrow cells involved in neovascularization

Circ Res. 2006 Apr 14;98(7):897-904. doi: 10.1161/01.RES.0000218193.51136.ad. Epub 2006 Mar 16.

Abstract

Vascular endothelial cadherin (VE-cadherin) is expressed on vascular endothelial cells, which are involved in developmental vessel formation. However, it remains elusive how VE-cadherin-expressing cells function in postnatal neovascularization. To trace VE-cadherin-expressing cells, we developed mice expressing either green fluorescent protein or LacZ driven by VE-cadherin promoter using Cre-loxP system. Although VE-cadherin promoter is less active after birth than during embryogenesis in blood vessels, it is reactivated on cardiac ischemia. Both types of reporter-positive cells are found in the vasculature and in the infarcted myocardium. Those found in the vasculature were pre-existing endothelial cells and incorporated endothelial progenitor cells derived from extracardiac tissue. In addition to the vasculature, VE-cadherin promoter-activated cells were positive for CD45 in the bone marrow cells of the infarcted mice. VE-cadherin promoter-reactivated CD45-positive leukocytes were also found in the infarcted area. In addition, VE-cadherin promoter was activated in the bone marrow vessels of the infarcted mice. Collectively, our findings reveal a new ischemia-induced neovascularization mechanism involving VE-cadherin; the re-expressed VE-cadherin-mediated cell adhesion between cells may be involved not only in homing of bone marrow-derived cells to ischemic area but also mobilization from bone marrow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Blood Vessels / embryology*
  • Cadherins / genetics*
  • Embryonic Development
  • Endocardium / embryology
  • Endothelium, Vascular / physiology*
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Heart / embryology*
  • Integrases / metabolism
  • Mice
  • Mice, Transgenic
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / physiopathology*
  • Myocardial Revascularization
  • Pregnancy
  • Promoter Regions, Genetic

Substances

  • Antigens, CD
  • Cadherins
  • cadherin 5
  • Cre recombinase
  • Integrases