Critical role of scavenger receptor-BI-expressing bone marrow-derived endothelial progenitor cells in the attenuation of allograft vasculopathy after human apo A-I transfer.
Allograft vasculopathy is the leading cause of death in patients with heart transplantation. Accelerated endothelial regeneration mediated by enhanced endothelial progenitor cell (EPC) incorporation may attenuate the development of allograft vasculopathy. We investigated the hypothesis that modulation of EPC biology and attenuation of allograft vasculopathy by increased high-density lipoprotein cholesterol after human apo A-I (AdA-I) transfer requires scavenger receptor (SR)-BI expression in bone marrow-derived EPCs. After AdA-I transfer, the number of circulating EPCs increased 2.0-fold (P < .001) at different time points in C57BL/6 mice transplanted with SR-BI(+/+) bone marrow but remained unaltered in mice with SR-BI(-/-) bone marrow. The effect of high-density lipoprotein on EPC migration in vitro requires signaling via SR-BI and extracellular signal-regulated kinases and is dependent on increased nitric oxide (NO) production in EPCs. Human apo A-I transfer 2 weeks before paratopic artery transplantation reduced intimal area at day 21 3.7-fold (P < .001) in mice with SR-BI(+/+) bone marrow but had no effect in mice with SR-BI(-/-) bone marrow. AdA-I transfer potently stimulated EPC incorporation and accelerated endothelial regeneration in chimeric SR-BI(+/+) mice but not in chimeric SR-BI(-/-) mice. In conclusion, human apo A-I transfer accelerates endothelial regeneration mediated via SR-BI expressing bone marrow-derived EPCs, thereby preventing allograft vasculopathy.
Feng
Yingmei
Y
Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
van Eck
Miranda
M
Van Craeyveld
Eline
E
Jacobs
Frank
F
Carlier
Vincent
V
Van Linthout
Sophie
S
Erdel
Martin
M
Tjwa
Marc
M
De Geest
Bart
B
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D001808:Blood Vessels / Q000473:pathology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002339:Carotid Arteries / Q000637:transplantation; D002465:Cell Movement; D008076:Cholesterol, HDL / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D012038:Regeneration; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism*; D014184:Transplantation, Homologous
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases