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Discovery of novel peptides targeting pro-atherogenic endothelium in disturbed flow regions-Targeted siRNA delivery to pro-atherogenic endothelium in vivo

Title
Discovery of novel peptides targeting pro-atherogenic endothelium in disturbed flow regions-Targeted siRNA delivery to pro-atherogenic endothelium in vivo
Authors
Chung J.Shim H.Kim K.Lee D.Kim W.J.Kang D.H.Kang S.W.Jo H.Kwon K.
Ewha Authors
강상원권기환심현보김관창정지화강동훈
SCOPUS Author ID
강상원scopus; 권기환scopus; 심현보scopus; 김관창scopus; 정지화scopus; 강동훈scopus
Issue Date
2016
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 6
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Atherosclerosis occurs preferentially in arterial regions exposed to disturbed blood flow. Targeting these pro-atherogenic regions is a potential anti-atherogenic therapeutic approach, but it has been extremely challenging. Here, using in vivo phage display approach and the partial carotid ligation model of flow-induced atherosclerosis in mouse, we identified novel peptides that specifically bind to endothelial cells (ECs) exposed to disturbed flow condition in pro-atherogenic regions. Two peptides, CLIRRTSIC and CPRRSHPIC, selectively bound to arterial ECs exposed to disturbed flow not only in the partially ligated carotids but also in the lesser curvature and branching point of the aortic arch in mice as well as human pulmonary artery branches. Peptides were conjugated to branched polyethylenimine-polyethylene glycol polymer to generate polyplexes carrying siRNA targeting intercellular adhesion molecule-1 (siICAM-1). In mouse model, CLIRRTSIC polyplexes carrying si-ICAM-1 specifically bound to endothelium in disturbed flow regions, reducing endothelial ICAM-1 expression. Mass spectrometry analysis revealed that non-muscle myosin heavy chain II A (NMHC IIA) is a protein targeted by CLIRRTSIC peptide. Further studies showed that shear stress regulates NMHC IIA expression and localization in ECs. The CLIRRTSIC is a novel peptide that could be used for targeted delivery of therapeutics such as siRNAs to pro-atherogenic endothelium.
DOI
10.1038/srep25636
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자연과학대학 > 생명과학전공 > Journal papers
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