Cardiovascular Research Advance Access [Accepted Manuscript] published online on December 7, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm093
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Absence of CD36 Protects Against Atherosclerosis in ApoE Knock-Out Mice with no Additional Protection Provided by Absence of Scavenger Receptor AI/II
Department of Cell Biology, Cleveland Clinic, Cleveland, OH 44195
* Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021
Address Correspondence to: Maria Febbraio, Ph.D., Department of Cell Biology, Cleveland Clinic, 9500 Euclid Ave., NC-10, Cleveland, OH 44195, tel: 216-445-5605, fax: 216-444-9404, email: febbram{at}ccf.org
Aims: The role of scavenger receptors in atherogenesis is controversial as a result of conflicting reports and a recent hypothesis suggesting that scavenger receptor absence would enhance the pro-inflammatory, pro-atherogenic milieu. This study addresses the effect of combined absence of scavenger receptors CD36 and SRA I/II on atherosclerosis lesion development in the apolipoprotein E knock-out (apoEo) model.
Methods: We created background-related strains of apoEo, scavenger receptor A I/II knock-out (SRAo)/apoEo, CD36 knock-out (CD36o)/apoEo and CD36o/SRAo/apoEo mice that were greater than 99% C57Bl/6. Four-week-old mice were fed a Western diet for 12 weeks and were assessed for lesion burden/morphology, risk factors for atherosclerosis, inflammatory mediators and macrophage function.
Results: There was a 61% and 74% decrease in total aortic lesion area in CD36oapoEo males and females, respectively, compared with apoEo controls. Absence of SRA was protective (32% decrease in lesion) in female mice. Combined absence of CD36 and SRA provided no further protection in either gender. Macrophages from mice lacking CD36 had decreased pro-inflammatory characteristics and less migration to a pro-inflammatory stimulus. Plasma levels of cytokines/chemokines showed that CD36o/apoEo and CD36oSRAoapoEo mice had a less pro-inflammatory phenotype compared with apoEo and SRAoapoEo mice. Oblivious mice in the apoEo background ruled out potential "passenger gene" effects in the case of CD36.
Conclusion: These results provide new insights into the pro-atherogenic mechanisms of CD36 by implicating processes other than modified lipoprotein uptake.
Time for primary review: 36
# These authors contributed equally.
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