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- W1984976110 abstract "<h3>Objectives</h3> Scavenger receptor BI (SR-BI) is a key regulator of high density lipoprotein (HDL) metabolism. Recent studies showed that mice deficient in SR-BI exhibit impaired erythropoiesis and it has been proposed that the high cholesterol environment plays a major role in the abnormal erythropoiesis. In this study, we<i> observed </i>the effect of SR-BI deficiency and hypercholesterolemia on erythropoiesis. <h3>Methods</h3> Three animal models were utilised to <i>evaluate</i> the role of SR-BI and hypercholesterolemia in erythropoiesis. 1. First, we used a high fat diet-induced hypercholesterolemia model. High fat diet caused a 2-fold increase in plasma cholesterol levels in SR-BI<sup>+/+</sup> (170 mg/dl to 352 mg/dl) and SR-BI<sup>-/-</sup> mice (315 mg/dl to 718 mg/dl). 2. Then, we used SR-BI/LDLR double knockout mice to further elucidate the contribution of hypercholesterolemia to erythropoiesis. 3. Finally, we investigated the contribution of hepatic SR-BI using ScarbI<sup>I179N</sup> mutant mice, whose hepatic SR-BI expression has been knocked down by 90% and therefore has a 1.7-fold increase in plasma cholesterol levels compared to wild type controls. <h3>Results</h3> The high fat diet treatment markedly exacerbated the impaired erythropoiesis in SR-BI<sup>-/-</sup> mice as shown by 4-fold increase in reticulocyte percentage and 2.5-fold increase in early-to-late erythroblast ratio. Unexpectedly, high fat feeding did not induce abnormal erythropoiesis in SR-BI<sup>+/+</sup> mice despite of hypercholesterolemia in these mice. SR-BI/LDLR double knockout mice had 2-fold increase in plasma cholesterol levels and exhibited severer impaired erythropoiesis, similar to high fat-fed SR-BI<sup>-/-</sup> mice. Interestingly, despite of hyperlipidemia, LDLR single knockout mice did not display impaired erythropoiesis. ScarbI<sup>I179N</sup> mice displayed normal erythropoiesis, similar to wild type controls. These findings indicate that hypercholesterolemia does not cause abnormal erythropoiesis in the presence of SR-BI, but markedly impairs erythropoiesis in the absence of SR-BI. <h3>Conclusions</h3> Our study suggest that SR-BI is essential for normal erythropoiesis, and that hypercholesterolemia and SR-BI deficiency synergistically exacerbated impaired erythropoiesis<sub>.</sub>" @default.
- W1984976110 created "2016-06-24" @default.
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- W1984976110 date "2013-08-01" @default.
- W1984976110 modified "2023-09-26" @default.
- W1984976110 title "GW24-e0058 Effects of SR-BI Deficiency and Hypercholesterolemia on Erythropoiesis" @default.
- W1984976110 doi "https://doi.org/10.1136/heartjnl-2013-304613.216" @default.
- W1984976110 hasPublicationYear "2013" @default.
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