title: Autotaxin-Lysophosphatidic Acid Axis Acts Downstream of Apoprotein B Lipoproteins in Endothelial Cells.
abstract: As they travel through the blood stream, plasma lipoproteins interact continuously with endothelial cells (ECs). Although the focus of research has mostly been guided by the importance of lipoproteins as risk factors for atherosclerosis, thrombosis, and other cardiovascular diseases, little is known about the mechanisms linking lipoproteins and angiogenesis under physiological conditions, and particularly, during embryonic development. In this work, we performed global mRNA expression profiling of endothelial cells from hypo-, and hyperlipidemic zebrafish embryos with the goal of uncovering novel mediators of lipoprotein signaling in the endothelium.
  
  
  
  Microarray analysis was conducted on fluorescence-activated cell sorting-isolated fli1:EGFP(+) ECs from normal, hypo-, and hyperlipidemic zebrafish embryos. We found that opposed levels of apoprotein B lipoproteins result in differential expression of the secreted enzyme autotaxin in ECs, which in turn affects EC sprouting and angiogenesis. We further demonstrate that the effects of autotaxin in vivo are mediated by lysophosphatidic acid (LPA)-a well-known autotaxin activity product-and that LPA and LPA receptors participate as well in the response of ECs to lipoprotein levels.
  
  
  
  Our findings provide the first in vivo gene expression profiling of ECs facing different levels of plasma apoprotein B lipoproteins and uncover a novel lipoprotein-autotaxin-LPA axis as regulator of EC behavior. These results highlight new roles for lipoproteins as signaling molecules, which are independent of their canonical function as cholesterol transporters.
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Liron
authors: L
authors: Gibbs-Bar
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Hanoch
authors: H
authors: Tempelhof
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Rotem
authors: R
authors: Ben-Hamo
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Yona
authors: Y
authors: Ely
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Alexander
authors: A
authors: Brandis
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Roy
authors: R
authors: Hofi
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Gabriella
authors: G
authors: Almog
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Tslil
authors: T
authors: Braun
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Ester
authors: E
authors: Feldmesser
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E).
authors: Sol
authors: S
authors: Efroni
authors: From the Department of Biological Regulation (L.G.-B., H.T., Y.E., K.Y.), Department of Biological Services (E.F., A.B.), Department of Veterinary Services (R.H., G.A.), and Department of Molecular Genetics (T.B.), Weizmann Institute of Science, Rehovot, Israel; and Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel (R.B.-H., S.E). karina.yaniv@weizmann.ac.il.
authors: Karina
authors: K
authors: Yaniv
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology*; D020869:Gene Expression Profiling / Q000379:methods; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D008246:Lysophospholipids / Q000097:blood / Q000378:metabolism*; D009154:Mutation; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000099189:Lysophospholipase D
chemical_list: D001055:Apolipoproteins B; D049452:Green Fluorescent Proteins; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000099189:Lysophospholipase D; C000598206:Fli1b protein, zebrafish; C485184:enhanced green fluorescent protein; C032881:lysophosphatidic acid
keywords: autotaxin; cardiovascular disease; lipoproteins; lysophosphatidic acid; zebrafish