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Synergistically Combined Gene Delivery for Enhanced VEGF Secretion and Antiapoptosis

Title
Synergistically Combined Gene Delivery for Enhanced VEGF Secretion and Antiapoptosis
Author
이민형
Keywords
Gene delivery; Heme oxygenase-1; SHP-1; VEGF; microRNA; PAM-ABP; MICROVASCULAR ENDOTHELIAL-CELLS; PROTEIN-TYROSINE-PHOSPHATASE; HEME OXYGENASE-1; GROWTH-FACTOR; HINDLIMB ISCHEMIA; SIRNA DELIVERY; RAT MODEL; IN-VIVO; ANGIOGENESIS; EXPRESSION
Issue Date
2013-10
Publisher
AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Citation
MOLECULAR PHARMACEUTICS, 2013, 10(10), P.3676-3683
Abstract
With current pharmacological treatments, preventing the remodeling of the left ventricle and the progression to heart failure is a difficult task. Gene therapy is considered to provide a direct treatment to the long-term complications of ischemic heart diseases. Although current gene therapies that use single molecular targets seem potentially possible, they have not achieved success in the treatment of ischemic diseases. With an efficient polymeric gene carrier, PAM-ABP, we designed a synergistically combined gene-delivery strategy to enhance vascular endothelial growth factor (VEGF) secretion and to prolong its antiapoptotic effects. A hypcoxia-inducible plasmid expressing both hypoxia-inducible heme oxygenase-1 (HO-1) and the Src homology domain-2 containing tyrosine phosphatase-1 microRNA (miSHP-1) as well as a hypoxia-responsive VEGF plasmid were combined in this study. The positive feedback circuit between HO-1 and VEGF and the negative regulatory role of SHP-1 in angiogenesis enhance VEGF secretion synergistically. The synergy in VEGF secretion as a consequence of the gene combination and prolonged HO-1 activity was confirmed in hypoxic cardiomyocytes and cardiomyocyte apoptosis under hypoxia and was decreased synergistically. These results suggest that the synergistic combination of VEGF, HO-1, and miSHP-1 may be promising for the clinical treatment of ischemic diseases.
URI
https://pubs.acs.org/doi/abs/10.1021/mp400178mhttp://hdl.handle.net/20.500.11754/44567
ISSN
1543-8384; 1543-8392
DOI
10.1021/mp400178m
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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