PhD Scientific Days 2020

Theoretical and Translational IV. Lectures

Thromboxane A2 Mediates C3a-induced Vasoconstriction in Mouse and Human Coronary Arteries

Előadó neve

Dr. Kerkovits, Nóra Melinda

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

06305535777

Előadó e-mail címe

kerkovits.nora@med.semmelweis-univ.hu

Az előadás címe

Thromboxane A2 Mediates C3a-induced Vasoconstriction in Mouse and Human Coronary Arteries

Szerző(k) neve és munkahelye

Nóra Melinda Kerkovits1, Éva Ruisanchez1, Gábor Szénási1, Zoltán Benyó1
1 Institute of Translational Medicine, Semmelweis University, Budapest

Szekció

Theoretical and Translational IV. Lectures

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction. Several recent reports indicate a marked crosstalk between innate immunity and vasoregulation. Anaphylatoxins C3a and C5a have been reported to induce vasoactive effects, but the mechanism of their actions is obscure. Earlier studies reported increased plasma levels of C3a in cadiovascular diseases, especially pulmonary hypertension. Therefore, complement activation may contribute to changes of the vascular tone and reactivity under pathophysiological conditions.

Aims. In our present study we investigated the effects of C3a, the cleavage product of C3, the most abundant complement protein of the human circulation, on the arterial tone and blood pressure as well as the signaling pathways involved.

Materials and methods. Thoracic aortic segments were isolated from adult male C57Bl/6 wild type (WT) and knockout (KO) mice deficient in either thromboxane prostanoid receptor (TP KO) or cyclooxygenase 1 (COX1 KO). Human coronary arteries were obtained from the recipient hearts of patients undergoing transplantation for ischemic heart disease and/or dilated cardiomyopathy. Isometric tension changes of vascular segments were measured via myography and quantitated as percent of reference contraction induced by 124 mM K+.

Results. C3a (63-77), a specific C3a receptor agonist, evoked a pronounced vasoconstriction in WT vessels, which effect remained unaltered in the absence of endothelium. The vessels of COX1 KO mice showed a decreased response, and the C3a fragment caused a similarly reduced constriction in TP KO vessels. The vasoconstrictor effect of the peptide was remarkable in human coronary arteries, and was abolished by the pharmacological inhibition of COX1 and TP.

Conclusions. Our experiments indicate that C3a causes vasoconstriction in a non-endothelium-dependent manner, and this effect is mediated by COX1 and TP. These results propose that C3a-mediated vasoconstriction is mediated by smooth muscle derived thromboxane A2. These results altogether indicate that C3a is involved in the regulation of vascular tone and/or reactivity via stimulating thromboxane A2 release.

Grant support: NVKP_16-1-2016-0042 and EFOP-3.6.3-VEKOP-16-2017-00009.

Additional Information

Supervisor: Zoltán Benyó
benyo.zoltan@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4806

Start

12:25

End

12:40

Authors (legacy)

Nóra Melinda Kerkovits1, Éva Ruisanchez1, Gábor Szénási1, Zoltán Benyó1
1 Institute of Translational Medicine, Semmelweis University, Budapest