Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Myeloid Kdm6b deficiency results in advanced atherosclerosis

Neele, Annette E ; Gijbels, Marion J J ; van der Velden, Saskia ; Hoeksema, Marten A ; Boshuizen, Marieke C S ; Prange, Koen H M ; Chen, Hung-Jen ; Van den Bossche, Jan ; van Roomen, Cindy P P A and Shami, Annelie LU orcid , et al. (2018) In Atherosclerosis 275. p.156-165
Abstract

BACKGROUND AND AIMS: Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells. Given the importance of these cells in atherosclerosis, we now studied the effect of myeloid Kdm6b on disease progression.

METHODS: Bone marrow of myeloid Kdm6b deficient (Kdm6bdel) mice or wild type littermates (Kdm6bwt) was transplanted to lethally irradiated Ldlr-/- mice fed a high fat diet for 9... (More)

BACKGROUND AND AIMS: Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells. Given the importance of these cells in atherosclerosis, we now studied the effect of myeloid Kdm6b on disease progression.

METHODS: Bone marrow of myeloid Kdm6b deficient (Kdm6bdel) mice or wild type littermates (Kdm6bwt) was transplanted to lethally irradiated Ldlr-/- mice fed a high fat diet for 9 weeks to induce atherosclerosis.

RESULTS: Lesion size was similar in Kdm6bwt and Kdm6bdel transplanted mice. However, lesions of Kdm6bdel mice contained more collagen and were more necrotic. Pathway analysis on peritoneal foam cells showed that the pathway involved in leukocyte chemotaxis was most significantly upregulated. Although macrophage and neutrophil content was similar after 9 weeks of high fat diet feeding, the relative increase in collagen content and necrosis revealed that atherosclerotic lesions in Kdm6bdel mice progress faster.

CONCLUSION: Myeloid Kdm6b deficiency results in more advanced atherosclerosis.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Aorta/enzymology, Aortic Diseases/enzymology, Atherosclerosis/enzymology, Cells, Cultured, Chemotaxis, Leukocyte, Collagen/metabolism, Diet, High-Fat, Disease Models, Animal, Disease Progression, Female, Fibrosis, Foam Cells/enzymology, Jumonji Domain-Containing Histone Demethylases/deficiency, Macrophages, Peritoneal/enzymology, Mice, Inbred C57BL, Mice, Knockout, Necrosis, Neutrophil Infiltration, Plaque, Atherosclerotic, Receptors, LDL/deficiency, Time Factors
in
Atherosclerosis
volume
275
pages
156 - 165
publisher
Elsevier
external identifiers
  • scopus:85048328199
  • pmid:29908485
ISSN
1879-1484
DOI
10.1016/j.atherosclerosis.2018.05.052
language
English
LU publication?
no
additional info
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
id
8e5d9889-b724-4f11-bca2-0ea9320f3a23
date added to LUP
2025-01-22 15:23:44
date last changed
2025-04-17 10:36:49
@article{8e5d9889-b724-4f11-bca2-0ea9320f3a23,
  abstract     = {{<p>BACKGROUND AND AIMS: Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells. Given the importance of these cells in atherosclerosis, we now studied the effect of myeloid Kdm6b on disease progression.</p><p>METHODS: Bone marrow of myeloid Kdm6b deficient (Kdm6bdel) mice or wild type littermates (Kdm6bwt) was transplanted to lethally irradiated Ldlr-/- mice fed a high fat diet for 9 weeks to induce atherosclerosis.</p><p>RESULTS: Lesion size was similar in Kdm6bwt and Kdm6bdel transplanted mice. However, lesions of Kdm6bdel mice contained more collagen and were more necrotic. Pathway analysis on peritoneal foam cells showed that the pathway involved in leukocyte chemotaxis was most significantly upregulated. Although macrophage and neutrophil content was similar after 9 weeks of high fat diet feeding, the relative increase in collagen content and necrosis revealed that atherosclerotic lesions in Kdm6bdel mice progress faster.</p><p>CONCLUSION: Myeloid Kdm6b deficiency results in more advanced atherosclerosis.</p>}},
  author       = {{Neele, Annette E and Gijbels, Marion J J and van der Velden, Saskia and Hoeksema, Marten A and Boshuizen, Marieke C S and Prange, Koen H M and Chen, Hung-Jen and Van den Bossche, Jan and van Roomen, Cindy P P A and Shami, Annelie and Levels, Johannes H M and Kroon, Jeffrey and Lucas, Tina and Dimmeler, Stefanie and Lutgens, Esther and de Winther, Menno P J}},
  issn         = {{1879-1484}},
  keywords     = {{Animals; Aorta/enzymology; Aortic Diseases/enzymology; Atherosclerosis/enzymology; Cells, Cultured; Chemotaxis, Leukocyte; Collagen/metabolism; Diet, High-Fat; Disease Models, Animal; Disease Progression; Female; Fibrosis; Foam Cells/enzymology; Jumonji Domain-Containing Histone Demethylases/deficiency; Macrophages, Peritoneal/enzymology; Mice, Inbred C57BL; Mice, Knockout; Necrosis; Neutrophil Infiltration; Plaque, Atherosclerotic; Receptors, LDL/deficiency; Time Factors}},
  language     = {{eng}},
  pages        = {{156--165}},
  publisher    = {{Elsevier}},
  series       = {{Atherosclerosis}},
  title        = {{Myeloid Kdm6b deficiency results in advanced atherosclerosis}},
  url          = {{http://dx.doi.org/10.1016/j.atherosclerosis.2018.05.052}},
  doi          = {{10.1016/j.atherosclerosis.2018.05.052}},
  volume       = {{275}},
  year         = {{2018}},
}