Myeloid Kdm6b deficiency results in advanced atherosclerosis

Annette E Neele, Marion J J Gijbels, Saskia van der Velden, Marten A Hoeksema, Marieke C S Boshuizen, Koen H M Prange, Hung-Jen Chen, Jan Van den Bossche, Cindy P P A van Roomen, Annelie Shami, Johannes H M Levels, Jeffrey Kroon, Tina Lucas, Stefanie Dimmeler, Esther Lutgens, Menno P J de Winther

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalAtherosclerosis
Volume275
DOIs
Publication statusPublished - Aug 2018

Cite this

Neele, A. E., Gijbels, M. J. J., van der Velden, S., Hoeksema, M. A., Boshuizen, M. C. S., Prange, K. H. M., ... de Winther, M. P. J. (2018). Myeloid Kdm6b deficiency results in advanced atherosclerosis. Atherosclerosis, 275, 156-165. https://doi.org/10.1016/j.atherosclerosis.2018.05.052