Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 20, Issue 3, Pages 721-727Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.20.3.721
Keywords
adenovirus; HDL; receptors, lipoprotein; recombinant protein
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R37HL055323, R01HL055323, P01HL041484] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-55323, HL-41484] Funding Source: Medline
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HDL cholesterol levels in humans are inversely correlated with the risk of atherosclerosis. The class B scavenger receptor type I (SR-BI) is the first molecularly well-defined HDL receptor, and hepatic overexpression of SR-BI in normal mice has been shown to result in decreased plasma HDL cholesterol levels. To determine whether SR-BI overexpression is proatherogenic or is protective against atherosclerosis, LDL receptor-deficient mice were placed on a high-fat/high-cholesterol diet for 2 or 12 weeks to induce atherosclerotic lesions of different stages and then were injected with a recombinant adenovirus encoding murine SR-BI. Transient hepatic overexpression of SR-BI in mice with both early and advanced lesions significantly decreased atherosclerosis. SR-BI expression was associated with markedly decreased HDL cholesterol and either unchanged or only modestly reduced non-HDL cholesterol levels; in all experiments, the mean HDL cholesterol levels were significantly correlated with atherosclerotic lesion size. These data suggest that interventions that promote HDL cholesterol transport and lower plasma HDL cholesterol levels can suppress atherosclerosis, even when initiated after significant lesion development. Thus, stimulation of hepatic SR-BI activity may provide a novel target for therapeutic intervention in atherosclerotic cardiovascular disease.
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