Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease.
Scavenger receptors act as membrane-bound and soluble proteins that bind to macromolecular complexes and pathogens. This diverse supergroup of proteins mediates binding to modified lipoprotein particles which regulate the initiation and progression of atherosclerotic plaques. In vascular tissues, scavenger receptors are implicated in regulating intracellular signaling, lipid accumulation, foam cell development, and cellular apoptosis or necrosis linked to the pathophysiology of atherosclerosis. One approach is using gene therapy to modulate scavenger receptor function in atherosclerosis. Ectopic expression of membrane-bound scavenger receptors using viral vectors can modify lipid profiles and reduce the incidence of atherosclerosis. Alternatively, expression of soluble scavenger receptors can also block plaque initiation and progression. Inhibition of scavenger receptor expression using a combined gene therapy and RNA interference strategy also holds promise for long-term therapy. Here we review our current understanding of the gene delivery by viral vectors to cells and tissues in gene therapy strategies and its application to the modulation of scavenger receptor function in atherosclerosis.
Stephen
Sam L
SL
Endothelial Cell Biology Unit, Institute of Molecular & Cellular Biology, LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK.
Freestone
Katie
K
Dunn
Sarah
S
Twigg
Michael W
MW
Homer-Vanniasinkam
Shervanthi
S
Walker
John H
JH
Wheatcroft
Stephen B
SB
Ponnambalam
Sreenivasan
S