PhD Scientific Days 2020

Theoretical and Translational IV. Posters

Role of the LPC-ATX-LPA Pathway in the Development of Endothelial Dysfunction

Előadó neve

Dr. Majer, Aliz

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36308295753

Előadó e-mail címe

majeraliz@gmail.com

Az előadás címe

Role of the LPC-ATX-LPA Pathway in the Development of Endothelial Dysfunction

Szerző(k) neve és munkahelye

Aliz Majer1, Anna Janovicz1, Lili Balogh1, Andrea Balogh1, Gábor Tigyi2,1, Zoltán Benyó1 and Éva Ruisanchez1

1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary;
2Department of Physiology, University of Tennessee Health Science Center, Memphis, USA

Szekció

Theoretical and Translational IV. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Lysophosphatidylcholine (LPC) is a component of the oxidized low-density lipoprotein that plays a major role in the development of atherosclerosis. LPC impairs endothelium-dependent vasorelaxation through decreasing the bioavailability of NO. Although LPC can be hydrolyzed into lysophosphatidic acid (LPA) by the lysophospholipase autotaxin (ATX), the involvement of this pathway in the development of LPC-elicited endothelial dysfunction has not been evaluated yet.

Methods: Myographic experiments were performed on thoracic aorta segments isolated from adult male C57Bl6 and LPA1, LPA2, LPA4, LPA5 receptor knock out (KO) mice. The effect of LPC (10 µM) or LPA (10 µM) on the NO-dependent vasorelaxation was measured after a 20 min incubation. The vessels were pre-contracted using phenylephrine (PE) prior to exposure to increasing concentrations of acetylcholine (ACh) to evoke vasorelaxation. In some experiments, the ATX inhibitor GLPG1690 (10 µM) was added to the baths, 10 min prior to the administration of LPC. To evaluate the expression of ATX in the aortic tissue, we used immunohistochemical staining .

Results: We confirmed the presence of ATX in the aortic endothelium. LPC significantly attenuated the ACh-induced vasorelaxation, in addition LPA treatment was also able to evoke endothelial dysfunction. The ATX inhibitor GLPG1690 diminished the effect of LPC and interestingly, it was more pronounced in the aortic arch as compared to the distal aorta. In addition, the effect of LPC developed in the LPA1, LPA2, and LPA4 KO mice, but was decreased in the LPA5 KO mice.

Conclusions: Our study shows that ATX and LPA play an important role in the development of LPC-elicited endothelial dysfunction and the involvement of this pathway is more pronounced in the aortic arch. Furthermore, LPA appears to mediate this effect via LPA5 receptors. Clinical evidence indicates that the development of atherosclerotic lesions is more pronounced and progressive in the aortic arch, thus the LPC-ATX-LPA5 axis might contribute to the progression of this disease.

Supported by the Hungarian NRDIO (K-112964, 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.

Additional Information

Supervisors: Éva Ruisanchez (ruisanchez.eva@med.semmelweis-univ.hu), Zoltán Benyó (benyo.zoltan@med.semmelweis-univ.hu)

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4812

Start

12:43

End

12:46

Authors (legacy)

Aliz Majer1, Anna Janovicz1, Lili Balogh1, Andrea Balogh1, Gábor Tigyi2,1, Zoltán Benyó1 and Éva Ruisanchez1

1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary;
2Department of Physiology, University of Tennessee Health Science Center, Memphis, USA