Macrophage PLTP is atheroprotective in LDLr-deficient mice with systemic PLTP deficiency.
J Lipid Res
; 49(1): 24-32, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-17928634
ABSTRACT
Systemic phospholipid transfer protein (PLTP) is a recognized risk factor for coronary heart disease. In apolipoprotein E-deficient mice, systemic PLTP deficiency is atheroprotective, whereas PLTP overexpression is proatherogenic. As expected, we also observed significantly smaller lesions (P < 0.0001) in hypercholesterolemic double mutant low density lipoprotein receptor-deficient (LDLr(-/-)) PLTP-deficient (PLTP(-/-)) mice compared with LDLr(-/-) mice expressing systemic PLTP. To assess the specific contribution of only macrophage-derived PLTP to atherosclerosis progression, bone marrow transplantation was performed in LDLr(-/-) mice that also lacked systemic PLTP. Groups of double mutant PLTP(-/-)LDLr(-/-) mice were irradiated with 1,000 rad and injected with bone marrow (BM) cells collected from either PLTP(-/-) or wild-type mice. When fed a high-fat diet, BM cell expression of PLTP decreased plasma cholesterol of PLTP(-/-)LDLr(-/-) mice from 878 +/- 220 to 617 +/- 183 mg/dl and increased HDL cholesterol levels from 54 +/- 11 to 117 +/- 19 mg/dl. This decreased total plasma cholesterol and increased HDL cholesterol contributed to the significantly smaller atherosclerotic lesions in both aortas and heart sinus valves observed in these mice. Thus, unlike total systemic PLTP, locally produced macrophage-derived PLTP beneficially alters lipoprotein metabolism and reduces lesion progression in hyperlipidemic mice.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Colesterol
/
Apolipoproteína A-I
/
Proteínas de Transferência de Fosfolipídeos
/
Aterosclerose
/
Hipercolesterolemia
/
Macrófagos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos