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Updated: Aug 26, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Depletion of natural killer cell function decreases atherosclerosis in low-density lipoprotein receptor null mice
Stewart C Whitman1, Debra L Rateri, Stephen J Szilvassy
1Departments of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, 40 Ruskin St, Room H259A, Ottawa, Ontario, Canada, K1Y 4W7. swhitman@ottawaheart.ca
Objective:
Natural killer (NK) cells are a key component of innate immunity. Despite being identified in human and mouse atherosclerotic lesions, the role of NK cells in the disease process in unknown. To determine this role, we created chimeric atherosclerosis-susceptible low-density lipoprotein (LDL) receptor null (ldl-r-/-) mice that were deficient in functional NK cells through expression of a transgene encoding for Ly49A.
Methods And Results:
Bone marrow cells from Ly49A transgenic and nontransgenic littermates were used to repopulate the hematopoietic system of lethally-irradiated female ldl-r-/- mice. After a recovery period to permit sufficient engraftment, mice were placed on a diet enriched in saturated fat and cholesterol. After 8 weeks, there was no difference in either serum total cholesterol concentrations or lipoprotein cholesterol distribution in mice repopulated with nontransgenic versus Ly49A transgenic marrow cells. Using immunohistochemistry, we detected NK cells in atherosclerotic lesions of both groups of mice. However, deficiency of functional NK cells significantly reduced the size of atherosclerosis by 70% (P=0.0002) in cross-sectional analysis of the aortic root and by 38% (P=0.004) in en face analysis of the intimal surface of the aortic arch.
Conclusions:
These studies demonstrate that NK cells infiltrate the vessel wall and promote atherosclerotic lesion development.
Insights
Natural killer (NK) cells promote atherosclerosis development. Removing functional NK cells significantly reduced lesion size in mice, demonstrating their role in cardiovascular disease progression.
Area of Science:
- Immunology
- Cardiovascular Research
- Innate Immunity
Background:
- Natural killer (NK) cells are crucial for innate immunity.
- NK cells are found in atherosclerotic lesions, but their role is unclear.
Purpose of the Study:
- To investigate the role of NK cells in atherosclerosis.
- To create and study chimeric mice lacking functional NK cells.
Main Methods:
- Created chimeric low-density lipoprotein receptor null (ldl-r-/-) mice lacking functional NK cells using Ly49A transgenic bone marrow.
- Fed mice a high-fat, high-cholesterol diet for 8 weeks.
- Analyzed serum lipids and quantified atherosclerotic lesions via immunohistochemistry.
Main Results:
- No significant differences in serum cholesterol or lipoprotein distribution were observed.
- NK cells were detected in atherosclerotic lesions of both experimental groups.
- Deficiency in functional NK cells reduced atherosclerosis by 70% in the aortic root and 38% in the aortic arch.
Conclusions:
- NK cells infiltrate the vessel wall.
- NK cells actively promote the development of atherosclerotic lesions.
