Cardiac ischemia activates vascular endothelial cadherin promoter in both preexisting vascular cells and bone marrow cells involved in neovascularization.
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.
Department of Structural Analysis, National Cardiovascular Center Research Institute, Osaka, Japan.
Naoko
N
Kogata
Yuji
Y
Arai
James T
JT
Pearson
Kazuaki
K
Hashimoto
Kyoko
K
Hidaka
Tatsuya
T
Koyama
Satoshi
S
Somekawa
Yoshikazu
Y
Nakaoka
Minetaro
M
Ogawa
Ralf H
RH
Adams
Masato
M
Okada
Naoki
N
Mochizuki
D000818:Animals; D015703:Antigens, CD; D001808:Blood Vessels / Q000196:embryology*; D015820:Cadherins / Q000235:genetics*; D047108:Embryonic Development; D004699:Endocardium / Q000196:embryology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology*; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000235:genetics / Q000503:physiopathology*; D009204:Myocardial Revascularization; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D019426:Integrases; D000099152:Cadherin 5; C045073:Cre recombinase