Roles for lysophosphatidic acid signaling in vascular development and disease

Susan S. Smyth, Maria Kraemer, Liping Yang, Patrick Van Hoose, Andrew J. Morris

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The bioactive lipid lysophosphatidic acid (LPA) is emerging as an important mediator of inflammation in cardiovascular diseases. Produced in large part by the secreted lysophospholipase D autotaxin (ATX), LPA acts on a series of G protein-coupled receptors and may have action on atypical receptors such as RAGE to exert potent effects on vascular cells, including the promotion of foam cell formation and phenotypic modulation of smooth muscle cells. The signaling effects of LPA can be terminated by integral membrane lipid phosphate phosphatases (LPP) that hydrolyze the lipid to receptor inactive products. Human genetic variants in PLPP3, that predict lower levels of LPP3, associate with risk for premature coronary artery disease, and reductions of LPP3 expression in mice promote the development of experimental atherosclerosis and enhance inflammation in the atherosclerotic lesions. Recent evidence also supports a role for ATX, and potentially LPP3, in calcific aortic stenosis. In summary, LPA may be a relevant inflammatory mediator in atherosclerotic cardiovascular disease and heightened LPA signaling may explain the cardiovascular disease risk effect of PLPP3 variants.

Original languageEnglish
Article number158734
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1865
Issue number8
DOIs
StatePublished - Aug 2020

Bibliographical note

Publisher Copyright:
© 2020

Keywords

  • Autotaxin
  • Lipid phosphate phosphatase
  • Lysophosphatidic acid
  • Lysophospholipids

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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