CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells promotes atherogenesis in ApoE-deficient mice.
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.


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.
Zhao
Liang
L
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Lee
Eric
E
Zukas
Alicia M
AM
Middleton
Melissa K
MK
Kinder
Michelle
M
Acharya
Pinak S
PS
Hall
Jason A
JA
Rader
Daniel J
DJ
Puré
Ellen
E
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology*; D002465:Cell Movement; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology*; D005355:Fibrosis; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D036904:Leukocyte Rolling; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000276:immunology*; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D018183:Transplantation Chimera
D001057:Apolipoproteins E; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid