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Hindi Research Article
Absence of uPAR Protects against the Development of Atherosclerosis in LDL Receptor-Null Mice
*Corresponding Author:
Copyright: © 2015 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
We have previously identified unrokinase plasminogen activator receptor [uPAR] as one of several genes differentially induced in human aortic endothelial cells [HAEC] by Oxidized-L-alpha-1-Palmitoyl-2-Arachidonoyl-snglycero- 3-Phosphorylcholine [Ox-PAPC], which is a key biologically active component oxidized low-density lipoprotein [Ox-LDL]. The role of uPAR in the development of atherosclerosis is not known. In this report, we show that uPAR message and protein are induced in HAEC within hours of Ox-PAPC treatment. We developed uPAR-/- mice on an LDLR-/- background [uPAR-/-/LDLR-/-] and show that uPAR plays a proatherogenic role in the aortic vascular milieu. When compared to LDLR-/- mice, uPAR-/-/LDLR-/- mice fed a Western diet for 12 weeks had i] an anti-atherogenic serum lipid profile, ii] less atherogenic lipoproteins, iii] reduced accumulation of macrophages in the aortic sinus lesions, and iv] significantly reduced atherosclerosis in the entire aortic tree and the aortic sinus. Our results suggest, for the first time, that uPAR inhibition is a potential therapeutic approach to prevent atherosclerosis development.
