LPA receptor 4 deficiency attenuates experimental atherosclerosis

Liping Yang, Maria Kraemer, Xianjun Frank Fang, Peggi M. Angel, Richard R. Drake, Andrew J. Morris, Susan S. Smyth

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The widely expressed lysophosphatidic acid (LPA) selective receptor 4 (LPAR4) contributes to vascular development in mice and zebrafish. LPAR4 regulates endothelial permeability, lymphocyte migration, and hematopoiesis, which could contribute to atherosclerosis. We investigated the role of LPAR4 in experimental atherosclerosis elicited by adeno-associated virus expressing PCSK9 to lower LDL receptor levels. After 20 weeks on a Western diet, cholesterol levels and lipoprotein distribution were similar in WT male and Lpar4Y/ mice (P = 0.94). The atherosclerotic lesion area in the proximal aorta and arch was 25% smaller in Lpar4Y/ mice (P = 0.009), and less atherosclerosis was detected in Lpar4Y/ mice at any given plasma cholesterol. Neutral lipid accumulation in aortic root sections occupied 40% less area in Lpar4Y/ mice (P = 0.001), and CD68 expression was 25% lower (P = 0.045). No difference in -smooth muscle actin staining was observed. Bone marrow-derived macrophages isolated from Lpar4Y/ mice displayed significantly increased upregulation of the M2 marker Arg1 in response to LPA compared with WT cells. In aortic root sections from Lpar4Y/ mice, heightened M2 “repair” macrophage marker expression was detected by CD206 staining (P = 0.03). These results suggest that LPAR4 may regulate the recruitment of specific sets of macrophages or their phenotypic switching in a manner that could influence the development of atherosclerosis.

Original languageEnglish
Pages (from-to)972-980
Number of pages9
JournalJournal of Lipid Research
Volume60
Issue number5
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health Grant R01 HL120507 and US Department of Veterans Affairs Grant BX002769. Manuscript received 9 November 2018 and in revised form 14 February 2019. Published, JLR Papers in Press, February 22, 2019 DOI https://doi.org/10.1194/jlr.M091066

Publisher Copyright:
© 2019 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved.

Keywords

  • Lipid phosphate phosphatase
  • Lysophosphatidic acid
  • Lysophospholipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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