Human ApoA-I transfer attenuates transplant arteriosclerosis via enhanced incorporation of bone marrow-derived endothelial progenitor cells.
OBJECTIVE
Transplant arteriosclerosis is the leading cause of graft failure and death in patients with heart transplantation. Endothelial progenitor cells (EPCs) contribute to endothelial regeneration in allografts. We investigated whether increased HDL cholesterol induced by adenoviral human apoA-I (AdA-I) transfer increases number and function of EPCs, promotes incorporation of EPCs in Balb/c allografts transplanted paratopically in C57BL/6 ApoE-/- mice, and attenuates transplant arteriosclerosis.


RESULTS
EPC number in ApoE-/- mice was increased after AdA-I transfer as evidenced by 1.5-fold (P<0.01) higher Flk-1 Sca-1-positive cells and 1.4-fold (P<0.01) higher DiI-acLDL isolectin-positive spleen cells. In addition, HDL enhanced EPC function in vitro. Incorporation of bone marrow-derived EPCs was 5.8-fold (P<0.01) higher at day 21 after transplantation in AdA-I-treated apoE-/- mice compared with control mice. Enhanced endothelial regeneration in AdA-I-treated apoE-/- mice as evidenced by a 2.6-fold (P<0.01) increase of CD31-positive endothelial cells resulted in a 1.4-fold (P=0.059) reduction of neointima and a 3.9-fold (P<0.01) increase of luminal area.


CONCLUSIONS
Human apoA-I transfer increases the number of circulating EPCs, enhances their incorporation into allografts, promotes endothelial regeneration, and attenuates neointima formation in a murine model of transplant arteriosclerosis.
Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Yingmei
Y
Feng
Frank
F
Jacobs
Eline
E
Van Craeyveld
Christine
C
Brunaud
Jan
J
Snoeys
Marc
M
Tjwa
Sophie
S
Van Linthout
Bart
B
De Geest
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000502:physiology*; D008076:Cholesterol, HDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects / Q000502:physiology; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000502:physiology; D017539:Tunica Intima / Q000503:physiopathology
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL