Transplantation of monocyte CC-chemokine receptor 2-deficient bone marrow into ApoE3-Leiden mice inhibits atherogenesis.
Arterioscler Thromb Vasc Biol
; 23(3): 447-53, 2003 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-12615695
ABSTRACT
OBJECTIVE:
To determine the role of leukocyte CC-chemokine receptor 2 (CCR2) in the early development of atherosclerosis METHODS ANDRESULTS:
Bone marrow cells harvested from CCR2 (-/-) and CCR2 (+/+) mice were transplanted into ApoE3-Leiden mice, a mouse strain susceptible for diet-induced atherosclerosis. Eight weeks after bone marrow transplantation, the diet of regular chow was switched to a high-cholesterol diet (1% cholesterol, 15% fat, 0.5% cholate) for another 8 weeks to induce atherosclerosis. No significant differences in serum cholesterol and triglyceride levels were observed between the CCR2 (+/+) --> ApoE3-Leiden and CCR2 (-/-) --> ApoE3-Leiden mice. However, the mean cross-sectional aortic root lesion area of CCR2 (-/-) --> ApoE3-Leiden mice was only 2.94+/-1.94x10(4) microm2 compared with 20.94+/-12.71x10(4) microm2, for CCR2 (+/+) --> ApoE3-Leiden mice. Thus, the absence of CCR2 on leukocytes induces an 86% reduction of aortic lesion area as compared with controls (n=10, P<0.01).CONCLUSIONS:
These results provide direct evidence that CCR2 expressed by leukocytes plays a critical role in the initiation of early atherosclerosis and that pharmacological intervention in CCR2 function represents an attractive target to inhibit atherogenesis.
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Base de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
/
Arteriosclerosis
/
Médula Ósea
/
Trasplante de Médula Ósea
/
Receptores de Quimiocina
Límite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Países Bajos