Homing markers for atherosclerosis: applications for drug delivery, gene delivery and vascular imaging.
Endothelial dysfunction plays a major role in the pathogenesis of atherosclerosis. Pro-inflammatory cytokines such as interleukin-1 beta and tumour necrosis factor alpha activate endothelial cells changing their resting phenotype to become pro-adhesive, pro-thrombotic and pro-atherogenic. Phage display in vivo biopanning has been used to identify peptide sequences that home to diseased regions of the vessel wall in low density lipoprotein receptor (LDLr) knockout mice. In LDLr knockout mice, peptide sequence determinants exhibiting organ specificity have been isolated. These sequences have applications for gene delivery, drug delivery and for improving contrast agents for vascular imaging.
Cardiovascular Systems Unit, GlaxoWellcome Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK , pb6174@glaxowellcome.co.uk
P
P
Houston
J
J
Goodman
A
A
Lewis
C J
CJ
Campbell
M
M
Braddock
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D001435:Bacteriophages / Q000235:genetics; D001665:Binding Sites; D001667:Binding, Competitive; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein
D019151:Peptide Library; D010455:Peptides; D011973:Receptors, LDL