PhD Scientific Days 2025

Poster Session III. - K: Theoretical and Translational Medicine

Vasoactive Effects of Lysophosphatidic Acid in Murine Pulmonary Arteries

Name of the presenter

Varga Tamás

Institute/workplace of the presenter

Institute of Translational Medicine

Authors

Tamás Varga¹, Anna Monori-Kiss¹, Éva Ruisanchez¹, Bence Varga¹, Zoltán Benyó¹

1: Institute of Translational Medicine

Text of the abstract

Introduction: Lysophosphatidic acids (LPA) comprise a lipid mediator family with various vascular effects that they elicit via six specific, G-protein coupled receptors (LPAR1-6). Its dual vasoconstrictive and vasodilatative effects are thoroughly studied in murine aorta, where the polyunsaturated LPA species, among them the linoleoyl or 18:2 LPA, which is the most abundant LPA species in plasma, cause a NO-dependent decrease, and a prostanoid-dependent increase in vascular tone.
Aims: The investigation of the effects of 18:2 LPA on murine vascular tone, and the signal transduction pathways involved.
Methods: The vascular tone of the left and right extralobar pulmonary arteries prepared from C57Bl/6 mice was measured with wire myography. The investigation of the signal transduction pathways was carried out with pharmacological inhibitors, including the LPAR1/3 blocker Ki16425, the thromboxane prostanoid receptor antagonist SQ29548, and the non-selective nitric oxide synthase inhibitor l-NAME.
Results: 18:2 LPA caused significant vasoconstriction, but no vasodilation, in the murine pulmonary arteries. The effect was found to be independent of age, gender, and endothelial function. The response could be moderately augmented by phenylephrine induced precontraction. Ki16425 completely abolished LPA-induced vasoconstriction, whereas SQ29548 failed to alter it.
Conclusion: In murine pulmonary arteries, 18:2 LPA elicits a significant vasoconstrictive response without vasodilation. The receptor responsible for the effect might be LPAR1 or LPAR3, and the vasoconstriction is not mediated by the prostanoid pathway. The results, which point to basic differences compared to the LPA effects seen in murine aorta, implicate 18:2 LPA as a potential regulator of pulmonary circulation under physiological and pathophysiological conditions.
Funding: NRDN grants K-125174, K-135683, K-139230, Advanced-151053 and TKP 2021-EGA-25