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


ABSTRACT:

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.

SUBMITTER: White SJ 

PROVIDER: S-EPMC3206208 | biostudies-literature | 2011 Nov-Dec

REPOSITORIES: biostudies-literature

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

White Stephen J SJ   Sala-Newby Graciela B GB   Newby Andrew C AC  

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 20101012 6


<h4>Aims</h4>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.<h4>Methods</h4>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  ...[more]

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