期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 25, 期 7, 页码 1426-1432出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000167412.98221.1a
关键词
atherosclerosis; lipoproteins; HDL; apoA-I mimetic peptides; statins
资金
- NHLBI NIH HHS [HL-34343, P01 HL034343, HL-30568] Funding Source: Medline
Objectives-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 and Results-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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