Related Experiment Video
Updated: Feb 8, 2026
Three-Dimensional Imaging of Aortic Tissues in Atherosclerosis
Published on: October 25, 2024
Myeloid Kdm6b deficiency results in advanced atherosclerosis
Annette E Neele1, Marion J J Gijbels2, Saskia van der Velden1
1Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
Insights
Myeloid Kdm6b deficiency accelerates atherosclerosis progression. This epigenetic enzyme
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Immunology
Background:
- Atherosclerosis is a chronic inflammatory disease driven by lipids, with monocytes and macrophages central to its development.
- Macrophages transform into foam cells within arterial lesions by internalizing modified lipids.
- Previous work identified the epigenetic enzyme Kdm6b (Jmjd3) as a regulator of pro-fibrotic gene expression in peritoneal foam cells.
Purpose of the Study:
- To investigate the impact of myeloid Kdm6b on the progression of atherosclerosis.
- To determine if Kdm6b deficiency in myeloid cells influences the development of atherosclerotic lesions.
Main Methods:
- Bone marrow from Kdm6b-deficient or wild-type mice was transplanted into lethally irradiated Ldlr-/- mice.
- Recipients were fed a high-fat diet for 9 weeks to induce atherosclerosis.
- Atherosclerotic lesion characteristics and cellular composition were analyzed.
Main Results:
- Lesion size was comparable between Kdm6b-deficient and wild-type groups.
- Lesions in Kdm6b-deficient mice exhibited increased collagen content and necrosis.
- Pathway analysis revealed upregulation of leukocyte chemotaxis pathways in Kdm6b-deficient foam cells.
- Despite similar immune cell content, increased collagen and necrosis indicate accelerated lesion progression.
Conclusions:
- Myeloid Kdm6b deficiency leads to more advanced atherosclerotic lesions.
- The absence of myeloid Kdm6b promotes a more aggressive form of atherosclerosis.
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.
Related Concept Videos
01:26Atherosclerosis III: Management
01:30Atherosclerosis I: Introduction
01:27Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
01:23Atherosclerosis IV: Nursing Management
02:22Overview of Advanced Functional Groups
Functional groups are groups of atoms with specific chemical properties that occur within organic molecules and are sometimes denoted as “R”. Functional groups can “functionalize” a compound by enabling it to adopt different physical and chemical properties.
Types of Advanced Functional Groups
The table below summarizes some of the major functional groups in organic chemistry.
00:56Extraction: Advanced Methods