Topical HDL administration reduces vein graft atherosclerosis in apo E deficient mice.
Atherosclerosis
; 214(2): 271-8, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-20943224
ABSTRACT
OBJECTIVE:
Use of autologous vein grafts for surgical revascularisation is limited by vein graft failure. Topical high-density lipoprotein (HDL) administration on the adventitial side of vein grafts was evaluated as a new therapeutic modality to improve vein graft patency and function.METHODS:
Caval veins of C57BL/6 apo E(-/-) mice were grafted to the right carotid arteries of recipient 3 month-old C57BL/6 TIE2-LacZ/apo E(-/-) mice. HDL (200 µg/ml; 50 µl) in 20% pluronic F-127 gel was applied on the adventitial side of vein grafts.RESULTS:
Topical HDL application reduced intimal area by 55% (p < 0.001) at day 28 compared to control mice. Blood flow quantified by micro magnetic resonance imaging at day 28 was 2.8-fold (p < 0.0001) higher in grafts of topical HDL treated mice than in control mice. Topical HDL potently reduced intimal inflammation and resulted in enhanced endothelial regeneration as evidenced by a 1.9-fold (p < 0.05) increase in the number of CD31 positive endothelial cells. HDL potently enhanced migration and adhesion of endothelial colony-forming cells (ECFCs) in vitro, and these effects were dependent on signaling via scavenger receptor-BI, extracellular signal-regulated kinases, and NO, and on increased ß1 integrin expression. Correspondingly, the number of CD31 ß-galactosidase double positive cells, reflecting incorporated circulating progenitor cells, was 3.9-fold (p < 0.01) higher in grafts of HDL treated mice than in control grafts.CONCLUSIONS:
Topical HDL administration on the adventitial side of vein grafts attenuates vein graft atherosclerosis via increased incorporation of circulating progenitor cells in the endothelium, enhanced endothelial regeneration, and reduced intimal inflammation.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
/
Venas Cavas
/
Aterosclerosis
/
Injerto Vascular
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Oclusión de Injerto Vascular
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Lipoproteínas HDL
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Atherosclerosis
Año:
2011
Tipo del documento:
Article
País de afiliación:
Bélgica