P.30 Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice

Jeremy Lagrange; Stefanie Finger; Sabine Kossmann; Venkata Garlapati; Wolfram Ruf; Philip Wenzel

doi:10.2991/artres.k.201209.043

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Volume 26, Issue Supplement 1, December 2020, Pages S53 - S53

P.30 Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice

Authors

Jeremy Lagrange¹^{, 2}^{, *}, Stefanie Finger², Sabine Kossmann²^{, 3}^{, 4}, Venkata Garlapati², Wolfram Ruf²^{, 5}, Philip Wenzel²^{, 3}

¹INSERM 1116

²Center for Thrombosis and Hemostasis, University Medical Center Mainz

³Center for Cardiology– Cardiology I, University Medical Center Mainz

⁴The Heart Research Institute

⁵Department of Immunology and Microbial Science, Scripps Research

^*Corresponding author. Email: jeremy.lagrange@inserm.fr

Corresponding Author

Jeremy Lagrange

Available Online 31 December 2020.

DOI: 10.2991/artres.k.201209.043 How to use a DOI?
Keywords: LRP8; CMLV; AngII; anerysm
Abstract: Background/Objectives: Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was to evaluate the role of LRP8, in particular from immune cells, in the development of vascular inflammation.

Methods: LRP8^+/+ and LRP8^−/− mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day for 7 to 28 day) using osmotic minipumps. Blood pressure was recorded using tail cuff measurements. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging. Histological analysis of aortic sections was conducted using sirius red staining.

Results: AngII infusion worsened endothelial-dependent vascular relaxation and immune cells rolling and adherence to the carotid artery in both LRP8^+/+ as well as LRP8^−/− mice. However, only LRP8^−/− mice demonstrated a drastically increased mortality rate in response to AngII due to aortic dissection. Bone marrow transplantation revealed that chimeras with LRP8 deficient myeloid cells phenocopied LRP8^−/− mice.

Conclusion: AngII-infused LRP8 deficient mice could be a useful animal model to study aortic dissection reflecting the lethality of this disease in humans.
Copyright: © 2020 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

REFERENCES

[1]P Wenzel, M Knorr, S Kossmann, J Stratmann, M Hausding, S Schuhmacher, et al., Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction, Circulation, Vol. 124, 2011, pp. 1370-81.

[2]S Kossmann, J Lagrange, S Jäckel, K Jurk, M Ehlken, T Schönfelder, et al., Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension, Sci. Transl. Med., 2017, pp. 9.

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Journal: Artery Research
Volume-Issue: 26 - Supplement 1
Pages: S53 - S53
Publication Date: 2020/12/31
ISSN (Online): 1876-4401
ISSN (Print): 1872-9312
DOI: 10.2991/artres.k.201209.043 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Cite this article

ris enw bib

TY  - JOUR
AU  - Jeremy Lagrange
AU  - Stefanie Finger
AU  - Sabine Kossmann
AU  - Venkata Garlapati
AU  - Wolfram Ruf
AU  - Philip Wenzel
PY  - 2020
DA  - 2020/12/31
TI  - P.30 Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
JO  - Artery Research
SP  - S53
EP  - S53
VL  - 26
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.201209.043
DO  - 10.2991/artres.k.201209.043
ID  - Lagrange2020
ER  -

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