PhD Scientific Days 2025

Poster Session II. - J: Theoretical and Translational Medicine

Cellular Mechanism of C3a-induced Vasoconstriction in Mice

Name of the presenter

Kosztelnik Mónika

Institute/workplace of the presenter

Institute of Translational Medicine

Authors

Monika Kosztelnik¹, Balázs Besztercei², Anna Janovicz¹, Éva Ruisanchez¹, Zoltán Benyó¹

1: Institute of Translational Medicine, Semmelweis University; HUN-REN-SE Cerebrovascular and Neurocognitive Disease Research Group
2: Institute of Translational Medicine, Semmelweis University;

Text of the abstract

Introduction: Elevated plasma levels of C3a anaphylatoxin have been described in several inflammatory diseases, including atherosclerosis, myocardial ischaemia and hypertension. Our previous experiments have shown that, under physiological conditions, macrophages and their C3a receptors play a key role in the vascular response. Preliminary data demonstrate a correlation between the vasoconstrictor effect of C3a and the expression of the macrophage marker F4/80 in vascular segments. This correlation disappears after removal of the adventitia, suggesting that the vasoactive effect is mediated by perivascular resident macrophages.
Aims: The objective of the present study is to clarify the role of perivascular macrophages in C3a-induced vasoconstriction.
Methods: Macrophage depletion was conducted via diphtheria toxin-induced depletion in CD11b-DTR adult animals. To induce systemic inflammation, angiotensin II-containing osmotic pumps were implanted into the animals for a 14-day period. Isometric tension of the isolated vascular segments were measured using myography. The aortic expression of C3aR was determined with conventional qPCR and flow cytometry.
Results: Macrophage depleted aortic vessels showed decreased expression of C3aR and these vessels showed a decreased response to C3a compared to controls. Our qPCR and flow cytometry analysis revealed that the Ang II infusion increased the expression of F4/80 and C3aR in the aortas, especially in the adventitia. The removal of adventitia, or the absence of macrophages, resulted in a diminished response of blood vessels to C3a or ATII.
Conclusion: Our results indicate that the absence of CD11b positive macrophages leads to a decreased vasoconstrictor response to C3a and a decreased expression of C3aR in the aortic wall. The angiotensin-amplified C3a-induced vasoconstrictor effect was inhibited by macrophage depletion or adventitial detachment, suggesting that C3a anaphylatoxin and adventitial macrophages play a pivotal role in the progression of the diseases mentioned in the introduction. Elucidation of the cellular and molecular interactions may facilitate the identification of potential therapeutic targets to impede the onset and progression of these cardiovascular diseases.

Funding: NKFIH K-125174, K-135683, K-139230, K-151053, 2020-1.1.6-JÖVŐ-2021-00010, TKP2021-EGA-25, 2024-2.1.1-EKÖP-2024-00004