TY - JOUR
T1 - Myeloid Kdm6b deficiency results in advanced atherosclerosis
AU - Neele, Annette E
AU - Gijbels, Marion J J
AU - van der Velden, Saskia
AU - Hoeksema, Marten A
AU - Boshuizen, Marieke C S
AU - Prange, Koen H M
AU - Chen, Hung-Jen
AU - Van den Bossche, Jan
AU - van Roomen, Cindy P P A
AU - Shami, Annelie
AU - Levels, Johannes H M
AU - Kroon, Jeffrey
AU - Lucas, Tina
AU - Dimmeler, Stefanie
AU - Lutgens, Esther
AU - de Winther, Menno P J
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85048328199&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29908485
U2 - https://doi.org/10.1016/j.atherosclerosis.2018.05.052
DO - https://doi.org/10.1016/j.atherosclerosis.2018.05.052
M3 - Article
C2 - 29908485
SN - 0021-9150
VL - 275
SP - 156
EP - 165
JO - Atherosclerosis
JF - Atherosclerosis
ER -