on October 14, 2004
Published online before print October 14, 2004, doi: 10.1161/01.ATV.0000148007.06370.68
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Submitted on September 17, 2003
Accepted on October 7, 2004
Stem Cell Transplantation Reveals That Absence of Macrophage CD36 Is Protective Against Atherosclerosis
Maria Febbraio *;
From the Department of Cell Biology (M.F., R.L.S.), Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio; and the Department of Medicine (E.G.), Division of Hematology/Medical Oncology, Weill Medical College of Cornell University, New York, NY.
* To whom correspondence should be addressed. E-mail: febbram{at}ccf.org.
Objective--CD36 is expressed on multiple cell types and has numerous functions, a subset of which can impact on atherogenesis. In previous work, we demonstrated that CD36 absence was protective against lesion formation. The current objective was to determine whether absence of macrophage CD36 alone was protective.
Methods and Results--Lethal irradiation and stem cell transfer were used to create chimeric mice that did or did not express macrophage CD36 in the context of the Apo E-null model of atherosclerosis. After engraftment, mice were fed a Western diet for 12 weeks. White cell counts, plasma levels of lipoproteins, triacylglycerol, and nonesterified fatty acids were determined, and glucose tolerance tests were preformed. Lesion area was assessed quantitatively after oil red O staining. Mice lacking CD36 in macrophages alone were profoundly protected against atherosclerosis (88.1% reduction of lesion area throughout the aortic tree). Re-introduction of macrophage CD36 resulted in a 2.11-fold increase in lesion area. There were no differences in engraftment, macrophage recruitment, glucose tolerance, weight, and total, low-density lipoprotein, and high-density lipoprotein cholesterol among the groups. Lesions contained similar percent macrophage antigen-positive area.
Conclusion--Protection in this model is primarily caused by loss of CD36 macrophage function.
Key words: CD36 • atherosclerosis • Apo E-null mice • scavenger receptor • macrophages
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