Lipoprotein-derived lysophosphatidic acid promotes atherosclerosis by releasing CXCL1 from the endothelium.
| Title: | Lipoprotein-derived lysophosphatidic acid promotes atherosclerosis by releasing CXCL1 from the endothelium. |
|---|---|
| Authors: | Zhou Z; Institute for Molecular Cardiovascular Research, RWTH Aachen University, Germany.; Subramanian P; Sevilmis G; Globke B; Soehnlein O; Karshovska E; Megens R; Heyll K; Chun J; Saulnier-Blache JS; Reinholz M; van Zandvoort M; Weber C; Schober A |
| Source: | Cell metabolism [Cell Metab] 2011 May 04; Vol. 13 (5), pp. 592-600. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cambridge, Mass. : Cell Press, c2005- |
| MeSH Terms: | Hyperlipidemias*; Atherosclerosis/*chemically induced ; Atherosclerosis/*metabolism ; Chemokine CXCL1/*metabolism ; Endothelium, Vascular/*metabolism ; Lipoproteins, LDL/*metabolism ; Lysophospholipids/*pharmacology; Apolipoproteins E/physiology ; Carotid Arteries/cytology ; Carotid Arteries/drug effects ; Carotid Arteries/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/drug effects ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Monocytes/cytology ; Monocytes/drug effects ; Monocytes/metabolism ; RNA, Small Interfering/genetics ; Receptors, Lysophosphatidic Acid/antagonists & inhibitors ; Receptors, Lysophosphatidic Acid/genetics ; Receptors, Lysophosphatidic Acid/metabolism ; Animals ; Cells, Cultured ; Diet, Atherogenic ; Mice ; Mice, Inbred C57BL ; Mice, Knockout |
| Abstract: | Oxidatively modified low-density lipoprotein (oxLDL) plays a key role in the initiation of atherosclerosis by increasing monocyte adhesion. The mechanism that is responsible for the oxLDL-induced atherogenic monocyte recruitment in vivo, however, still remains unknown. Oxidation of LDL generates lysophosphatidylcholine, which is the main substrate for the lysophosphatidic acid (LPA) generating enzyme autotaxin. We show that oxLDL requires endothelial LPA receptors and autotaxin to elicit CXCL1-dependent arterial monocyte adhesion. Unsaturated LPA releases endothelial CXCL1, which is subsequently immobilized on the cell surface and mediates LPA-induced monocyte adhesion. Local and systemic application of LPA accelerates the progression of atherosclerosis in mice. Blocking the LPA receptors LPA(1) and LPA(3) reduced hyperlipidemia-induced arterial leukocyte arrest and atherosclerosis in the presence of functional CXCL1. Thus, atherogenic monocyte recruitment mediated by hyperlipidemia and modified LDL crucially depends on LPA, which triggers endothelial deposition of CXCL1, revealing LPA signaling as a target for cardiovascular disease treatments.; (Copyright © 2011 Elsevier Inc. All rights reserved.) |
| Substance Nomenclature: | 0 (Apolipoproteins E); 0 (Chemokine CXCL1); 0 (Cxcl1 protein, mouse); 0 (Lipoproteins, LDL); 0 (Lysophospholipids); 0 (RNA, Small Interfering); 0 (Receptors, Lysophosphatidic Acid); PG6M3969SG (lysophosphatidic acid) |
| Entry Date(s): | Date Created: 20110503 Date Completed: 20110905 Latest Revision: 20220316 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.cmet.2011.02.016 |
| PMID: | 21531341 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't