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Updated: Jul 5, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells promotes atherogenesis in ApoE-deficient
Liang Zhao1, Eric Lee, Alicia M Zukas
1The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Insights
CD44 on both immune and non-immune cells promotes atherosclerosis. This molecule also influences the balance between inflammation and fibrous cap formation in atherosclerotic lesions.
Area of Science:
- Immunology
- Cardiovascular Biology
- Cell Biology
Background:
- Atherosclerosis is a chronic inflammatory disease.
- CD44 is a cell surface receptor involved in cell adhesion and migration.
- The specific roles of CD44 on different cell types in atherosclerosis are not fully understood.
Purpose of the Study:
- To differentiate the contributions of CD44 expressed on bone marrow-derived cells versus non-bone marrow-derived cells to atherosclerosis.
- To investigate the role of CD44 in immune cell recruitment and vascular inflammation.
- To explore the impact of CD44 on the balance between inflammation and fibrosis in atherosclerotic lesions.
Main Methods:
- Bone marrow chimeras were used to compare CD44 expression in different cell compartments in apoE-/- mice.
- In vitro assays assessed leukocyte-endothelial cell adhesion and transendothelial migration.
- Hyaluronan-dependent migration of vascular smooth muscle cells (VSMCs) was analyzed.
Main Results:
- CD44 on both bone marrow-derived and non-bone marrow-derived cells promotes atherosclerosis.
- CD44 mediates macrophage and T cell recruitment to atherosclerotic lesions.
- CD44 on endothelial cells (ECs), macrophages, and T cells enhances leukocyte adhesion and migration.
- CD44 on VSMCs regulates hyaluronan-dependent migration.
- Mice lacking CD44 in both compartments showed reduced inflammation and enhanced fibrous cap formation.
Conclusions:
- CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells contributes to atherosclerosis development in apoE-deficient mice.
- CD44 plays a critical role in regulating the balance between inflammation and fibrosis in atherosclerotic lesions.
- Targeting CD44 may offer therapeutic potential for modulating atherosclerosis progression and clinical outcomes.
Objective:
The purpose of this study was to distinguish the contributions of CD44 expressed on bone marrow-derived and non-bone marrow-derived cells to atherosclerosis.
Methods And Results:
Using bone marrow chimeras, we compared the contributions of CD44 expressed on bone marrow-derived cells versus non-bone marrow-derived cells to the vascular inflammation underlying atherosclerosis. We show that CD44 in both bone marrow-derived and non-bone marrow-derived compartments promotes atherosclerosis in apoE-/- mice and mediates macrophage and T cell recruitment to lesions in vivo. We also demonstrate that CD44 on endothelial cells (ECs) as well as on macrophages and T cells enhances leukocyte-endothelial cell adhesion and transendothelial migration in vitro. Furthermore, CD44 on vascular smooth muscle cells (VSMCs) regulates their hyaluronan (HA)-dependent migration. Interestingly, in mice lacking CD44 in both compartments, where we observed the least inflammation, we also observed enhanced fibrous cap formation.
Conclusions:
CD44 expressed on bone marrow-derived and non-bone marrow-derived cells both promote atherosclerosis in apoE-deficient mice. Furthermore, CD44 plays a pivotal role in determining the balance between inflammation and fibrosis in atherosclerotic lesions which can impact clinical outcome in humans.
