PhD Scientific Days 2022

Translational Medicine I. (Poster discussion will take place on the terrace of the room during the Coffee Break)

New Signaling Pathways of Lysophosphatidylcholine-Induced Endothelial Dysfunction

Előadó neve

Dr. Janovicz, Anna

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

+36304760018

Előadó e-mail címe

janovicz.anna11@gmail.com

Az előadás címe

New Signaling Pathways of Lysophosphatidylcholine-Induced Endothelial Dysfunction

Szerző(k) neve és munkahelye

Anna Janovicz1, Alíz Majer1, 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

Szóbeli

Szekció

Translational Medicine I. (Poster discussion will take place on the terrace of the room during the Coffee Break)

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 reportedly endothelial dysfunction, however the underlying mechanisms still remain elusive. LPC can be converted into lysophosphatidic acid (LPA) by the cell-surface enzyme autotaxin (ATX). In this study, we aimed to investigate the involvement of ATX and LPA in the LPC-induced endothelial dysfunction and to examine the molecular mechanisms behind this process.

Methods: Myograph experiments were performed on thoracic aorta segments isolated from adult male C57Bl6 (WT), LPA1, LPA2, LPA4 and LPA5 receptor 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 prior to exposure to increasing concentrations of acetylcholine to evoke vasorelaxation. Some of the vessels were pre-treated with ATX inhibitor GLPG1690 or superoxide-dismutase (SOD). In order to measure the quantity of extracelullar reactive oxygen species (ROS) released from LPC treated aortic segments, Amplex Red Assay was used.

Results: Endothelium-dependent vasorelaxation was attenuated by LPC, however the ATX inhibitor GLPG1690 significantly reduced this effect. The LPC-induced reduction of vasorelaxation remained unaltered in LPA1, LPA2 and LPA4 KO mice, but was decreased markedly in the segments isolated from LPA5 KO animals. Furthermore, LPC induced ROS release in WT vessels and SOD diminished the endothelial dysfunction in the presence of LPC. Interestingly, both of these effects appeared to be attenuated in vessels prepared from 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 ROS and this effect is likely to be mediated, at least in part, by LPA5 receptor. Taken together, in this study we identified a new pathway involved in the early stage of atherosclerosis.

Supported by the Hungarian NRDIO (K-125174, PD-132851, K-135683 and K-139230 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, Éva Ruisanchez

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4175

Start

09:30

End

09:45

Authors (legacy)

Anna Janovicz1, Alíz Majer1, 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