ApoA-I induced CD31 in bone marrow-derived vascular progenitor cells increases adhesion: implications for vascular repair.
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 microM 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.
Mythreye
Karthikeyan
K
Department of Medicine, Duke University Medical Center, 209 MSRB1 Research Drive, Durham, NC 27710, USA. mythreye.k@duke.edu
Satterwhite
Lisa L
LL
Davidson
W Sean
WS
Goldschmidt-Clermont
Pascal J
PJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D016632:Apolipoprotein A-I; D008055:Lipids; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005340:Fibrinogen
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