LOX-1: A potential target for therapy in atherosclerosis.

LOX-1: A potential target for therapy in atherosclerosis. Int J Biochem Cell Biol. 2017 Aug 28;: Authors: Arjuman A, Chandra NC Abstract Pro-inflammatory signal generated from the interaction of oxLDL with its cognate receptor LOX-1 has been attenuated successfully by a novel combination siRNA (siLOX-1(Ω)) targeting unique regions of Homo sapien LOX-1 mRNA. Signalling via LOX-1 was studied in a potentially pro-atherogenic arena recreated in a metabolic, pulse-chase set up. An initial pulse of oxLDL (20μg/mL;5h) was chased (without oxLDL) on a temporal scale upto 72h. Our study shows that the pro-inflammatory signal generated via oxLDL-LOX-1R interaction was mediated in two rungs, an initial sustained increase in LOX-1R expression up to 12h, and a renewal after 48h. TNF-α acted as a primary mediator of LOX-1R signalling, presumably also stimulating CD40 and MMP-9. Both TNF-α and IL-6 were involved in the second rung of LOX-1R signalling; maximum secretion of both was detected at 48h. Our study suggests a temporal sustenance of LOX-1 signalling by pro-inflammatory cytokines even on withdrawal of oxLDL. Also, siLOX-1(Ω) successfully abated LOX-1 expression along with its signalling intermediates, NO and NF-kB. Overall, LOX-1 signalling and the crucial role of cytokines in sustaining it is reported. Attenuation of this receptor may be of therapeutic value in atherosclerosis. PMID: 28860004 [PubMed - as supplied by publishe...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research