PhD Scientific Days 2026

Poster Session 3.R - Cardiovascular Medicine and Research

Angiotensin-induced Expansion of Vascular Macrophages and Its Reversal by Diphtheria Toxin-induced Cell Depletion in CD11b-DTR Transgenic Mice

Name of the presenter

Balázs, Villő

Institute/workplace of the presenter

Institute of Clinical Pathophysiology, Semmelweis University and VRG Therapeutics

Authors

Villő Balázs^1,2, Mia Jean Radics¹, Mónika Kosztelnik^1,3, Olivér Dinnyés¹, Imre Babay^1,3, Éva Ruisanchez^1,3, Mariann Kremlitzka², Zoltán Benyó^1,3
1: Institute of Clinical Pathophysiology, Semmelweis University, Budapest, Hungary
2: VRG Therapeutics Zrt., 1083 Budapest, Füvészkert utca 3., Hungary
3: HUN-REN-SE Cerebrovascular and Neurocognitive Disease Research Group, Budepest, Hungary

Text of the abstract

Introduction:
Cardiovascular diseases remain a leading cause of mortality worldwide, yet the precise molecular mechanisms of vascular inflammation are not fully elucidated. Beside its well-established roles in vasoconstriction and the regulation of electrolyte and fluid homeostasis, angiotensin II (AngII) can promote the release of various cytokines and chemokines. This inflammatory signalling cascade can contribute to adverse vascular remodelling, impaired endothelial function and pro-atherogenic structural alterations.
Aims:
To evaluate if Ang II treatment induces macrophage accumulation in the thoracic aorta, and analysed if this effect is reversible by macrophage depletion, through diphtheria toxin treatment in CD11b-DTR mice. This approach enable the elucidation of the mechanism of Ang II-mediate alteration of vascular functions.
Methods:
Ang II (520 ng/kg/min) was infused via subcutaneous osmotic minipumps for 14 days. Targeted macrophage depletion was achieved by administering diphtheria toxin (25 ng/g, i.p.) 48 and 24 hours prior to sacrifice in CD11b-DTR transgenic mice, which express the diphtheria toxin receptor under the control of the CD11b promoter. Layer-specific gene expression was quantified using RT-qPCR for myeloid markers F4/80 and CD11b.
Result:
Ang II infusion significantly increased F4/80 and CD11b expression across all aortic layers. The most pronounced accumulation was observed in the adventitia, identifying it as the primary site of macrophage recruitment. We observed the efficacy of the CD11b-DTR model, which achieved near-complete depletion of macrophages. Crucially, diphtheria toxin treatment effectively reversed Ang II-induced macrophage accumulation.
Conclusion:
By successfully employing the CD11b-DTR depletion model, we provide strong evidence that targeting macrophage accumulation can effectively mitigate Ang II-mediated vascular inflammation. Gaining a deeper insight into these inflammatory mechanisms has significant implications for understanding the pathogenesis of various cardiovascular diseases.
Funding:
Supported by the 2025-2.1.2-EKÖP-KDP-2025-00007 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund as well as the National Research, Development and Innovation Fund grants K-139230 and Advanced-151053.