Regulation of high-density lipoprotein on hematopoietic stem/progenitor cells in atherosclerosis requires scavenger receptor type BI expression.
Regulation of high-density lipoprotein on hematopoietic stem/progenitor cells in atherosclerosis requires scavenger receptor type BI expression.
复制标题
在动脉粥样硬化中调节造血干细胞/祖细胞上高密度脂蛋白需要清道夫受体型BI表达。
DOI：
10.1161/atvbaha.114.304006
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Feng Y
中科院分区：
文献类型：
--
作者：
Gao M;Zhao D;Schouteden S;Sorci-Thomas MG;Van Veldhoven PP;Eggermont K;Liu G;Verfaillie CM;Feng Y
Recently we demonstrated that scavenger receptor type BI (SR-BI), a HDL receptor, was expressed on murine hematopoietic stem/progenitor cells (HSPC) and infusion of reconstituted HDL and purified human apoA-I suppressed HSPC proliferation. We hypothesized that SR-B1 expression is required for the observed anti-proliferative effects of HDL on HSPC. SR-BI deficient (SR-BI−/−) mice and wild type (WT) controls were fed on chow or HFD (HFD) for 8–10 weeks. Under chow diet, a significant increase in Lin-Sca1+cKit+ cells (LSK cells, so called HSPC) was found in the BM of SR-BI−/− mice compared with WT mice. HFD induced a further expansion of CD150+CD48− LSK cells (HSCs), HSPCs, and granulocyte monocyte progenitors (GMPs) in SR-BI−/− mice. Injection of reactive oxygen species (ROS) inhibitor N-acetylcysteine attenuated HFD-induced HSPC expansion, leukocytosis and atherosclerosis in SR-BI−/− mice. ApoA-I infusion inhibited HSPC cell proliferation, Akt phosphorylation and ROS production in HSPC and plaque progression in low density lipoprotein receptor knockout (LDLr−/−) apoA-I−/− mice on HFD but had no effect on SR-BI−/− mice on HFD. Transplantation of SR-BI−/− BM cells into irradiated LDLr−/− recipients resulted in enhanced white blood cells (WBC) reconstitution, inflammatory cell production and plaque development. In patients with coronary heart disease, HDL levels were negatively correlated with WBC count and HSPC frequency in the peripheral blood. By flow cytometry, SR-BI expression was detected on human HSPC. SR-BI plays a critical role in the HDL-mediated regulation HSPC proliferation and differentiation which is associated with atherosclerosis progression.
