Poster Session K - Theoretical and Translational Medicine 2.
Dr. Janovicz, Anna
IWKDG6
Institute of Translational Medicine, Semmelweis University
+36304760018
janovicz.anna@semmelweis.hu
Sphingosine-1-Phosphate Evokes Vasorelaxation in Isolated Human Coronary Arteries
Anna Janovicz1,2, Aliz Majer1, Nóra Melinda Kerkovits1, Krisztina Eszter Vén1, Gábor J. Tigyi1,3, Bodo Levkau4, Tamás Radovits5, Béla Merkely5, Zsuzsanna Miklós1,6, Éva Ruisanchez1,2, Zoltán Benyó1,2
1: Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2: HUN-REN-SU Cerebrovascular and Neurocognitive Diseases Research Group, Budapest, Hungary
3: Department of Physiology, University of Tennessee Health Science Center, Memphis, USA
4: Institute of Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany
5: Heart and Vascular Center, Semmelweis University, Budapest, Hungary
6: National Korányi Institute for Pulmonology, Budapest, Hungary
Poszter
Poster Session K - Theoretical and Translational Medicine 2.
English
Theoretical and Translational Medicine
Introduction: Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid mediator with diverse functions in the cardiovascular system, including the regulation of vascular tone. S1P has been shown to have both vasodilator and vasoconstrictor effects in coronary arteries of different animal species; however little is known about its vasoactive properties in human vessels. Therefore, the aim of the current study was to examine the possible vasoactive effects of S1P in isolated human coronary arteries.
Methods: First and second diagonal branches of left anterior descending coronary arteries were isolated from explanted hearts of patients undergoing heart transplantation due to ischemic (IHD) or non-ischemic heart disease (non-IHD). Isometric tension changes were measured using wire-myography. S1P (1 µM) was applied to pre-contracted coronary segments. Some of the vessels were treated with S1P receptor 1 (S1PR1) inhibitor W146 (10 µM) or S1PR3 inhibitor TY52156 (10 µM), prior to S1P. For inhibition of eNOS enzymes, L-NAME (0.1 mM) was used. In some of the experiments, the vasoactive effect of S1PR1 agonist FTY720 (10 µM) was also tested.
Results: S1P induced a potent vasorelaxation (26.5±4.7%; n=19) in pre-contracted vessels isolated from patients with non-IHD. This effect was unaltered by the S1PR3 inhibitor TY52156 (25.5±5.3%; n=9); however, it was completely abolished by the S1PR1 antagonist W146 (4.8±1.4%; n=9). Furthermore, the S1PR1 agonist FTY720 evoked vasorelaxation (20.1±4.4%; n=9) similarly to S1P. The effect of S1P was diminished in endothelium-denuded arteries (0.1±0.05%; n=6), as well as in vessels treated with eNOS inhibitor L-NAME (4.1 ±1.2%; n=6). Interestingly, the S1P-induced vasorelaxation was reduced in coronary arteries obtained from IHD (10.2±2.4%; n=9) as compared to non-IHD patients.
Conclusions: Taken together, in this study, we described for the first time, that S1P evokes vasorelaxation in isolated human coronary arteries, in an S1PR1-, and eNOS-dependent manner. The results suggest, that this effect is independent of S1PR3 activation. Furthermore, the S1P-induced vasorelaxation is significantly diminished in IHD.
Funding: OTKA K-112964, K-125174, K-139230; ÚNKP-23-4-I, TKP2021-NVA-15, TKP2021-EGA-23.
Semmelweis University
Dr. Zoltán Benyó, Dr. Éva Ruisanchez
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
poszter
nem rendelkezett róla
4175
16:40
16:43