PhD Scientific Days 2024

Poster Session K - Theoretical and Translational Medicine 2.

Angiotensin II-Driven Systemic Inflammation Enhances C3a-Induced Vasoconstriction in Murine Models

Text of the abstract

Introduction: Our previous research has shown that the C3a receptor (C3aR) has been identified in various cell types within the mouse aortic wall, and our results indicate that the vasoconstrictive effect of the C3a anaphylatoxin is mediated by adventitial cells, likely macrophages.

Aims: This study aimed to explore the impact of chronic angiotensin II (Ang II) administration, a model of systemic inflammation, on C3a-induced vasoconstriction.

Method: Isometric tension changes in aortic segments of adult male C57BL/6 mice were measured using myography. Ang II or saline was delivered via osmotic pumps for two weeks at a dosage of 520 ng/kg/min. Gene expression levels of the C3AR1 anaphylatoxin receptor and macrophage markers (F4/80, CD68) in the aortic segments were quantified using real-time PCR. The localization of C3AR1 was confirmed via immunohistochemistry, and C3AR1 protein levels were quantified by Western blot analysis.

Results: Aortic segments from Ang II-treated mice demonstrated increased responsiveness to C3a compared to controls. Ang II infusion led to an upregulation of C3AR1 and macrophage marker expression, especially in the adventitia. Endothelium removal enhanced, whereas adventitia removal abolished, C3a-induced vasoconstriction. The response to C3a was also abolished by inhibitors of cyclooxygenase (COX) and thromboxane prostanoid (TP) receptors.

Conclusion: Our findings suggest that systemic inflammation amplifies C3a-induced vasoconstriction, mediated by thromboxane A2 release from adventitial macrophages. Targeting C3AR or TP receptors may be a promising therapeutic strategy to mitigate vascular dysfunction in systemic inflammatory diseases.

Funding: EFOP-3.6.3-VEKOP-16-2017-00009, OTKA K-139230, 2020-1.1.6-JÖVŐ-2021-00010, RRF-2.1.2.-12-2022-0001, and TKP2021-EGA-25.