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Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice

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 disease...

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Autores principales: Lagrange, Jeremy, Finger, Stefanie, Kossmann, Sabine, Garlapati, Venkata, Ruf, Wolfram, Wenzel, Philip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404218/
https://www.ncbi.nlm.nih.gov/pubmed/32664652
http://dx.doi.org/10.3390/ijms21144916
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author Lagrange, Jeremy
Finger, Stefanie
Kossmann, Sabine
Garlapati, Venkata
Ruf, Wolfram
Wenzel, Philip
author_facet Lagrange, Jeremy
Finger, Stefanie
Kossmann, Sabine
Garlapati, Venkata
Ruf, Wolfram
Wenzel, Philip
author_sort Lagrange, Jeremy
collection PubMed
description 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.
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spelling pubmed-74042182020-08-11 Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice Lagrange, Jeremy Finger, Stefanie Kossmann, Sabine Garlapati, Venkata Ruf, Wolfram Wenzel, Philip Int J Mol Sci Article 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. MDPI 2020-07-12 /pmc/articles/PMC7404218/ /pubmed/32664652 http://dx.doi.org/10.3390/ijms21144916 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lagrange, Jeremy
Finger, Stefanie
Kossmann, Sabine
Garlapati, Venkata
Ruf, Wolfram
Wenzel, Philip
Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
title Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
title_full Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
title_fullStr Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
title_full_unstemmed Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
title_short Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
title_sort angiotensin ii infusion leads to aortic dissection in lrp8 deficient mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404218/
https://www.ncbi.nlm.nih.gov/pubmed/32664652
http://dx.doi.org/10.3390/ijms21144916
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