Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:456-461
doi: 10.1161/hq0302.104905
doi: 10.1161/hq0302.104905
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Interleukin-4 Deficiency Decreases Atherosclerotic Lesion Formation in a Site-Specific Manner in Female LDL Receptor-/- Mice
From the Gill Heart Institute (V.L.K., A.D.), Division of Cardiovascular Medicine, and the Blood and Marrow Transplant Program (S.J.S.), Division of Hematology/Oncology, University of Kentucky, Lexington.
Correspondence to Alan Daugherty, PhD, Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY 40536. E-mail adaugh{at}pop.uky.edu
Activated lymphocytes and mast cells have been detected in human atherosclerotic lesions. Interleukin-4 (IL-4) is a prominent cytokine released during the activation of both these cell types, and its mRNA has been detected in human and mouse atherosclerotic lesions. To define the effects of IL-4 on atherogenesis, bone marrow stem cells from either IL-4-/- or IL-4+/+ mice were transplanted into lethally irradiated female low density lipoprotein (LDL) receptor-/- mice. After an interval sufficient to allow engraftment, mice were placed on a diet containing 21% saturated fat, 1.25% cholesterol, and 0.5% cholate. Hematopoietic engraftment was confirmed by the presence of the LDL receptor gene in bone marrow cells. The effect on IL-4 depletion was confirmed by quantifying cytokine release from splenocytes of reconstituted mice. The deficiency of IL-4 in bone marrow–derived cells had no effect on serum cholesterol concentrations or on the distribution of cholesterol among lipoproteins. Atherosclerotic lesion formation was not changed in the aortic root. However, deficiency of IL-4 led to reduced lesion size in the arch (9.1±1.1% versus 2.8±0.8% of intimal area, P<0.001) and the thoracic aorta (1.2±0.2% versus 0.4±0.1%, P<0.002). Therefore, IL-4 deficiency reduced atherosclerotic lesion formation in a site-specific manner in female LDL receptor-/- mice fed a high-fat diet.
Key Words: atherosclerosis • bone marrow transplant • interleukin-4 • low density lipoprotein receptors • T lymphocytes
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