Bristol Heart Institute, University of Bristol, Level 7 Bristol Royal Infirmary, Bristol BS2 8HW, UK.
Cardiovasc Pathol. 2011 Nov-Dec;20(6):369-73. doi: 10.1016/j.carpath.2010.08.007. Epub 2010 Oct 12.
The oxidized low-density lipoprotein receptor LOX-1 is up-regulated on activated endothelial cells, for example, the endothelium of atherosclerosis-prone sites, in both human and animal models. We examined whether endothelial LOX-1 overexpression may contribute to atherogenesis.
Adenoviral vectors expressing LOX-1 or LOXIN (a splice variant of LOX-1 with inhibitory function) were created and used to transduce the normally lesion-free common carotid artery, in high fat-fed female ApoE(-/-) mice. Mice were placed on high-fat diet for 4 weeks prior to gene transfer with either LOX-1 or a combination of LOX-1 and LOXIN, and assessment of plaque development analyzed 6 weeks following gene transfer.
Compared to controls, LOX-1 transduction induced a significant increase in plaque coverage within the common carotid artery to 91% compared to 50% after RAd66 control virus infection (P≤.05). This was inhibited by co-expression of LOXIN (62%).
These results demonstrate that up-regulation of LOX-1 promotes atherogenesis, highlighting LOX-1 function as a target for intervention. In addition, this study further demonstrated the inhibitory function of LOXIN.
氧化型低密度脂蛋白受体 LOX-1 在激活的内皮细胞（例如，动脉粥样硬化易损部位的内皮）中上调，在人类和动物模型中都是如此。我们研究了内皮细胞 LOX-1 的过表达是否可能导致动脉粥样硬化的发生。
构建了表达 LOX-1 或 LOXIN（具有抑制功能的 LOX-1 剪接变体）的腺病毒载体，并用于转导正常无病变的颈总动脉，在高脂肪喂养的雌性 ApoE（-/-）小鼠中。在基因转移前，用高脂肪饮食喂养小鼠 4 周，然后用 LOX-1 或 LOX-1 和 LOXIN 的组合进行基因转移，并在基因转移后 6 周评估斑块的形成。
与对照组相比，LOX-1 转导使颈总动脉内的斑块覆盖率显著增加，达到 91%，而 RAd66 对照病毒感染后为 50%（P≤0.05）。这一现象被 LOXIN 的共表达抑制（62%）。
这些结果表明，LOX-1 的上调促进了动脉粥样硬化的发生，突出了 LOX-1 作为干预靶点的功能。此外，这项研究进一步证明了 LOXIN 的抑制功能。
