Regulation of Lysophosphatidic Acid Metabolism and Signaling by Lipoproteins
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
See accompanying article on page 2058
In addition to their role in transporting cholesterol and triglycerides, plasma lipoprotein particles have been long known to promote signaling responses in many blood and vascular cell types. Some of these effects have been attributed to minor but potent bioactive lipid constituents. For example, oxidized phosphatidylcholines are inflammatory mediators that likely contribute to the development and progression of atherosclerosis that is driven by subendothelial accumulation of low-density lipoproteins.1 Similarly, some of the athero- and vasoprotective effects of high-density lipoproteins may be accounted for by the bioactive lipid sphingosine 1 phosphate that is carried on this class of lipoprotein particles in association with apolipoprotein M.2 A growing body of evidence implicates another bioactive lipid, lysophosphatidic acid (LPA) as a regulator of vascular development and pathologies. LPA is present in plasma bound to both lipoproteins and serum albumin. LPA-specific G-protein–coupled receptors expressed on vascular endothelial and smooth muscle cells regulate vascular permeability, inflammation, intimal hyperplasia (in the setting of vascular injury), and atherosclerosis.3 Although LPA is a ubiquitous intermediate in intracellular phospholipid synthesis, extracellular signaling LPA is primarily generated by a secreted lysophospholipase D called autotaxin.4 In this issue of the …