Luangrath Vilayphone, Brodeur Mathieu R, Rhainds David, Brissette Louise
Département des Sciences Biologiques, Université du Québec à Montréal, C.P. 8888, Succursale Centreville, Montréal, Québec, Canada.
Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1290-5. doi: 10.1161/ATVBAHA.107.161653. Epub 2008 Apr 24.
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.
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.
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.
分化簇36（CD36）是一种多功能蛋白，因其在体外具有摄取巨噬细胞中氧化型低密度脂蛋白（oxLDL）的能力而被人们所熟知，因此被认为具有致动脉粥样硬化作用。它也能结合低密度脂蛋白（LDL）。我们的目的是确定CD36在小鼠体内天然LDL和oxLDL代谢中的生理作用。
在野生型、CD36基因敲除（KO）、B类I型清道夫受体（SR-BI）基因敲除以及SR-BI/CD36双基因敲除小鼠中进行了标记LDL和oxLDL的清除研究。我们发现，CD36会阻碍天然LDL的清除，而有利于oxLDL的清除。这一点通过对野生型和CD36基因敲除小鼠肝细胞原代培养物进行的结合和降解试验得到了证实。此外，我们的体内研究表明，SR-BI和CD36在从oxLDL中选择性摄取胆固醇酯（CE）方面均不起重要作用，而在没有SR-BI的情况下，CD36可以从LDL中选择性摄取CE。
我们的研究首次表明，CD36在小鼠体内对oxLDL的摄取中起重要作用。由于CD36也会延缓LDL的清除，其致动脉粥样硬化特性可能也与其对LDL分解代谢的负面影响有关。
