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Hypocholesterolemia, foam cell accumulation, but no atherosclerosis in mice lacking ABC-transporter A1 and scavenger receptor BI
Y Zhao, M Pennings, CLJ Vrins, L Calpe-Berdiel... - Atherosclerosis, 2011 - Elsevier High-density lipoprotein (HDL) mediated reverse cholesterol transport (RCT) is regarded to be crucial for prevention of foam cell formation and atherosclerosis. ABC-transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) are involved in the biogenesis of HDL and the ...
High-density lipoprotein (HDL) mediated reverse cholesterol transport (RCT) is regarded to be crucial for prevention of foam cell formation and atherosclerosis. ABC-transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) are involved in the biogenesis of HDL and the selective delivery of HDL cholesterol to the liver, respectively. In the present study, we phenotypically characterized mice lacking these two proteins essential for HDL metabolism. ABCA1 SR-BI double knockout (d KO) mice showed severe hypocholesterolemia mainly due to HDL loss, despite a 90% reduction of HDL cholesterol uptake by liver. VLDL production was increased in d KO mice. However, non-HDL cholesterol levels were reduced, probably due to enhanced clearance via LRP1. Hepatobiliary cholesterol transport and fecal sterol excretion were not impaired in d KO mice. In contrast, the macrophage RCT in d KO mice was markedly impaired as compared to WT mice, associated with the accumulation of macrophage foam cells in the lung and Peyer's patches. Strikingly, no atherosclerotic lesion formation was observed in d KO mice. In conclusion, both ABCA1 and SR-BI are essential for maintaining a properly functioning HDL-mediated macrophage RCT, while the potential anti-atherosclerotic functions of ABCA1 and SR-BI are not evident in d KO mice due to the absence of pro-atherogenic lipoproteins.
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Hypocholesterolemia, foam cell accumulation, but no atherosclerosis in mice lacking ABC-transporter A1 and scavenger receptor BI |
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