Autotaxin-lysophosphatidic acid axis acts downstream of Apoprotein B lipoproteins in endothelial cells

Liron Gibbs-Bar, Hanoch Tempelhof, Rotem Ben-Hamo, Yona Ely, Alexander Brandis, Roy Hofi, Gabriella Almog, Tslil Braun, Ester Feldmesser, Sol Efroni, Karina Yaniv

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Objective - 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. Approach and Results - 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. Conclusions - 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.

Original languageEnglish
Pages (from-to)2058-2067
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume36
Issue number10
DOIs
StatePublished - 1 Oct 2016

Bibliographical note

Publisher Copyright:
© 2016 American Heart Association, Inc.

Keywords

  • autotaxin
  • cardiovascular disease
  • lipoproteins
  • lysophosphatidic acid
  • zebrafish

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