科研之友
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摘要
Transgenic over expression of apolipoprotein A-I (ApoA-I) the major structural apolipoprotein of HDL appears to convey the most consistent and strongest anti atherogenic effect observed in animal models so far. We tested the hypothesis that ApoA-I mediates its cardio protective effects additionally through ApoA-I induced differentiation of bone marrow-derived progenitor cells in vitro. This study demonstrates that lineage negative bone marrow cells (lin(-) BMCs) alter and differentiate in response to free ApoA-I. We find that lin- BMCs in culture treated with recombinant free ApoA-I at a concentration of 0.4 mu M are twice as large in size and have altered cell morphology compared to untreated cells; untreated cells retain the original spheroid morphology. Further, the total number of CD31 positive cells in the ApoA-I treated population consistently increased by two fold. This phenotype was significantly reduced in untreated cells and points towards a novel ApoA-I dependent differentiation. A protein lacking its best lipid-binding region (ApoA-I Delta 10) did not stimulate any changes in the lin(-)BMCs indicating that ApoA-I may mediate its effects by regulating cholesterol efflux. The increased CD31 correlates with an increased ability of the lin BMCs to adhere to both fibronectin and mouse brain endothelial cells. Our results provide the first evidence that exogenous free ApoA-I has the capacity to change the characteristics of progenitor cell populations and suggests a novel mechanism by which HDL may mediate its cardiovascular benefits. Published by Elsevier B.V.
- 出版日期2008-12
