Objective—The cluster of differentiation-36 (CD36) is a multifunctional protein which is recognized for its in vitro ability to take up oxidized low-density lipoproteins (oxLDL) in macrophages and is therefore considered atherogenic. It also binds LDL. Our objective was to define the physiological role of CD36 in both native LDL and oxLDL metabolism in mice.

Methods and Results—Clearance studies of labeled LDL and oxLDL were conducted in wild-type, CD36 knockout (KO), scavenger receptor class B, type I (SR-BI) KO, and SR-BI/CD36 double KO mice. We found that CD36 impedes the disappearance of native LDL and favors that of oxLDL. This was confirmed by association and degradation assays with primary cultures of hepatic cells from wild-type and CD36 KO mice. In addition, our in vivo work indicates that neither SR-BI nor CD36 plays a significant role in cholesteryl esters (CE) selective uptake (SU) from oxLDL, whereas CD36, in absence of SR-BI, can selectively take CE from LDL.

Conclusion—Our investigation showed for the first time that CD36 plays a significant role in oxLDL uptake in vivo in the mouse. As CD36 also retards LDL clearance, its atherogenic character may also relate to its negative effect on LDL catabolism.