D-4F and statins synergize to render HDL antiinflammatory in mice and monkeys and cause lesion regression in old apolipoprotein E-null mice.
Arterioscler Thromb Vasc Biol
; 25(7): 1426-32, 2005 Jul.
Article
en En
| MEDLINE
| ID: mdl-15845909
ABSTRACT
OBJECTIVE:
We tested for synergy between pravastatin and D-4F by administering oral doses of each in combination that were predetermined to be ineffective when given as single agents. METHODS ANDRESULTS:
The combination significantly increased high-density lipoprotein (HDL)-cholesterol levels, apolipoprotein (apo)A-I levels, paraoxonase activity, rendered HDL antiinflammatory, prevented lesion formation in young (79% reduction in en face lesion area; P<0.0001) and caused regression of established lesions in old apoE null mice (ie, mice receiving the combination for 6 months had lesion areas that were smaller than those before the start of treatment (P=0.019 for en face lesion area; P=0.004 for aortic root sinus lesion area). After 6 months of treatment with the combination, en face lesion area was 38% of that in mice maintained on chow alone; P<0.00004) with a 22% reduction in macrophage content in the remaining lesions (P=0.001), indicating an overall reduction in macrophages of 79%. The combination increased intestinal apoA-I synthesis by 60% (P=0.011). In monkeys, the combination also rendered HDL antiinflammatory.CONCLUSIONS:
These results suggest that the combination of a statin and an HDL-based therapy may be a particularly potent treatment strategy.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
/
Pravastatina
/
Apolipoproteína A-I
/
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Aterosclerosis
/
HDL-Colesterol
Límite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos