PhD Scientific Days 2021

TT_II_P: Theoretical and Translational Medicine II. Posters

Molecular Mechanisms of Lysophosphatidylcholine-Induced Endothelial Dysfunction

Előadó neve

Dr. Janovicz, Anna

Előadó munkahelye

Semmelweis University, Institute of Translational Medicine

Előadó telefonszáma

+36304760018

Előadó e-mail címe

janovicz.anna@med.semmelweis-univ.hu

Az előadás címe

Molecular Mechanisms of Lysophosphatidylcholine-Induced Endothelial Dysfunction

Szerző(k) neve és munkahelye

Anna Janovicz1, Alíz Majer1, Tímea Tóth1, Gábor Tigyi1,2, Zoltán Benyó1, Éva Ruisanchez1
1 Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2 Department of Physiology, University of Tennessee Health Science Center, Memphis, USA

Bemutatás módja

Poszter

Szekció

Theoretical and Translational Medicine II. Posters

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Endothelial dysfunction is an early symptom of atherosclerosis, characterized by reduced NO-dependent vasorelaxation. Lysophosphatidylcholine (LPC), a component of oxidized low-density lipoprotein can evoke endothelial dysfunction, however the underlying mechanisms still remain elusive. LPC can be converted into lysophosphatidic acid (LPA) by the cell-surface enzyme autotaxin (ATX). According to our previous results, LPA causes cyclooxigenase-1 (COX1) and thromboxane receptor (TP) mediated vasoconstriction.
Aims: Our aim was to investigate the involvement of ATX and LPA in the LPC-induced endothelial dysfunction and to study the molecular mechanisms behind this process.
Methods: Myograph experiments were performed on thoracic aorta segments isolated from adult male C57Bl6 (WT), LPA1, LPA2, LPA4, LPA5 receptor, TP receptor and COX1 enzyme knock out (KO) mice. The effect of LPC on the NO-dependent vasorelaxation was examined after a 20 min incubation. The vessels were pre-contracted using phenylephrine (PE) prior to exposure to increasing concentrations of acetylcholine to evoke vasorelaxation. Some of the vessels were pre-treated with ATX inhibitor GLPG1690 or the superoxide scavenger Tempol.
Results: Endothelium-dependent vasorelaxation was attenuated by LPC, however the ATX inhibitor GLPG1690 significantly reduced this effect. The effect of LPC was developed in COX1, TP, LPA1, LPA2 and LPA4 KO mice, but was markedly decreased in the segments isolated from LPA5 KO animals. On the other hand, Tempol diminished the endothelial dysfunction in the WT but it was not effective in the LPA5 KO mice.
Conclusions: We demonstrated that ATX and LPA play an important role in the development of LPC-induced endothelial dysfunction. Furthermore, LPA appear to mediate its effect via LPA5 receptor. The results suggest that the reduction of NO-dependent vasorelaxation is associated with elevated production of reactive oxigen species and this effect is likely to be mediated by LPA5 receptor. Taken together, in this study we identified a new pathway involved in the early steps of atherosclerosis.

Supported by the Hungarian NRDIO (K-125174, PD-132851 and NVKP_16-1-2016-0042 grants) as well as by the EFOP-3.6.3-VEKOP-16-2017-00009 grant.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Zoltán Benyó

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4175

Start

13:05

End

13:08

Authors (legacy)

Anna Janovicz1, Alíz Majer1, Tímea Tóth1, Gábor Tigyi1,2, Zoltán Benyó1, Éva Ruisanchez1
1 Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2 Department of Physiology, University of Tennessee Health Science Center, Memphis, USA