Overexpression of Scavenger Receptor LOX-1 in Endothelial Cells Promotes Atherogenesis in the ApoE(-/-) Mouse Model

Overview

Journal Cardiovasc Pathol

Specialties Cardiology & Vascular Diseases
Pathology

Date 2010 Oct 15

PMID 20943418

Citations 22

Authors

Stephen J White

Graciela B Sala-Newby

Andrew C Newby

Affiliations

Soon will be listed here.

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.

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