Cardiovascular Research Advance Access originally published online on December 7, 2007
Cardiovascular Research 2008 78(1):185-196; 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 A I/II
1 Department of Cell Biology, Cleveland Clinic, 9500 Euclid Ave., NC-10, Cleveland, OH 44195, USA
2 Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA
* Corresponding author. Tel: +1 216 445 5605; fax: +1 216 444 9404. E-mail address: 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 (apoE°) model.
Methods: We created background-related strains of apoE°, scavenger receptor A I/II knock-out (SRA°)/apoE°, CD36 knock-out (CD36°)/apoE°, and CD36°/SRA°/apoE° mice that were >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 CD36°/apoE° males and females, respectively, compared with apoE° controls. The absence of SRA was protective (32% decrease in lesion) in female mice. The 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 CD36°/apoE° and CD36°/SRA°/apoE° mice had a less pro-inflammatory phenotype compared with apoE° and SRA°/apoE° mice. Oblivious mice in the apoE° 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.
KEYWORDS CD36; Scavenger receptors; Macrophage; ApoE knock-out
Time for primary review: 36 days
These authors contributed equally.
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