Overexpression of scavenger receptor LOX-1 in endothelial cells promotes atherogenesis in the ApoE−/− mouse model

AIMS: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.