Macrophage PLTP is atheroprotective in LDLr-deficient mice with systemic PLTP deficiency
| Autor: | Joshua J. Bulgrien, David J. Bonnet, David T. Valenta, Linda K. Curtiss |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Apolipoprotein B Hypercholesterolemia Inflammation QD415-436 Biochemistry chemistry.chemical_compound Mice Endocrinology Internal medicine Phospholipid transfer protein medicine Animals Phospholipid Transfer Proteins Receptor Bone Marrow Transplantation biology Apolipoprotein A-I Cholesterol Macrophages Cell Biology bone marrow transplant low density lipoprotein receptor Mice Mutant Strains phospholipid transfer protein medicine.anatomical_structure chemistry Receptors LDL inflammation Low-density lipoprotein LDL receptor biology.protein lipids (amino acids peptides and proteins) Bone marrow medicine.symptom atherosclerosis |
| Zdroj: | Journal of Lipid Research, Vol 49, Iss 1, Pp 24-32 (2008) |
| ISSN: | 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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