Integrated Human Evaluation of the Lysophosphatidic Acid Pathway as a Novel Therapeutic Target in Atherosclerosis

Molecular Therapy. Methods & Clinical Development
Silvia AldiEva Hurt-Camejo

Abstract

Variants in the PLPP3 gene encoding for lipid phosphate phosphohydrolase 3 have been associated with susceptibility to atherosclerosis independently of classical risk factors. PLPP3 inactivates lysophosphatidic acid (LPA), a pro-inflammatory, pro-thrombotic product of phospholipase activity. Here we performed the first exploratory analysis of PLPP3, LPA, and LPA receptors (LPARs 1-6) in human atherosclerosis. PLPP3 transcript and protein were repressed when comparing plaques versus normal arteries and plaques from symptomatic versus asymptomatic patients, and they were negatively associated with risk of adverse cardiovascular events. PLPP3 localized to macrophages, smooth muscle, and endothelial cells (ECs) in plaques. LPAR 2, 5, and especially 6 showed increased expression in plaques, with LPAR6 localized in ECs and positively correlated to PLPP3. Utilizing in situ mass spectrometry imaging, LPA and its precursors were found in the plaque fibrous cap, co-localizing with PLPP3 and LPAR6. In vitro, PLPP3 silencing in ECs under LPA stimulation resulted in increased expression of adhesion molecules and cytokines. LPAR6 silencing inhibited LPA-induced cell activation, but not when PLPP3 was silenced simultaneously. Our results show...Continue Reading

References

Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y ZhengE J Goetzl
Aug 15, 2003·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·A R NaylorP R F Bell
Jun 16, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Volker BrinkmannTimothy Hla
Apr 8, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Birgitta RosengrenEva Hurt-Camejo
Nov 1, 2008·Bioinformatics·Andrew D JohnsonPaul I W de Bakker
Mar 25, 2010·Prostaglandins & Other Lipid Mediators·Mu-En LinJerold Chun
May 1, 2010·The American Journal of Pathology·Martine BotErik A L Biessen
Apr 23, 2011·Circulation. Cardiovascular Genetics·Christin StegemannManuel Mayr
Jul 28, 2012·Biochimica Et Biophysica Acta·H RenS S Smyth
Oct 30, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Manikandan PanchatcharamSusan S Smyth
May 15, 2013·Journal of Lipid Research·Ayca ErbilginAldons J Lusis
May 17, 2014·Nature Reviews. Drug Discovery·David CookMenelas N Pangalos
Nov 27, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Makoto KuranoYutaka Yatomi
Feb 24, 2015·Progress in Lipid Research·Sabin Llona-MinguezThomas Helleday
Mar 31, 2015·Journal of Lipid Research·Xiaoyun TangDavid N Brindley
Sep 9, 2015·Journal of Cell Science·Hiroshi YukiuraJunken Aoki
Dec 2, 2015·Journal of Internal Medicine·L PerisicU Hedin
Jul 30, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Ljubica Perisic MaticUlf Hedin
Oct 4, 2016·Cardiovascular Research·Zahia Touat-HamiciEwa Ninio
Oct 25, 2016·ACS Medicinal Chemistry Letters·Fabrizio GiordanettoEva Hurt-Camejo
Dec 13, 2016·European Journal of Preventive Cardiology·John M GregsonUNKNOWN EPIC-CVD consortium and the CHD Exome+ consortium
Feb 12, 2017·Angewandte Chemie·Eric ValeurAlleyn T Plowright

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Citations

Mar 9, 2019·International Journal of Molecular Sciences·Shi-Hui LawLiang-Yin Ke
Feb 24, 2019·Journal of Lipid Research·Liping YangSusan S Smyth
Jul 1, 2020·International Journal of Molecular Sciences·Eva Knuplez, Gunther Marsche
Apr 4, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Dawid S ChabowskiJulie K Freed
May 1, 2019·Journal of Lipid Research·Liping YangSusan S Smyth
Feb 21, 2019·ACS Medicinal Chemistry Letters·Robert W Johnson, Nari Talaty

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Datasets Mentioned

BETA
GSE21545

Methods Mentioned

BETA
SMA
genotyping
chips

Software Mentioned

BiKE
FTMSControl
GraphPad Prism
FlexImaging
MultiImaging

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