Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermo-responsive amphiphilic polymer in a rat myocardial infarction model.
Thermo-responsive hydrogel-mediated gene transfer may be preferred for the muscle, because the release of DNA into the surrounding tissue can be controlled by the 3-dimensional structure of the hydrogel. Such a system for the controlled release of a therapeutic gene may extend the duration of gene expression. Here, a thermo-responsive, biodegradable polymeric hydrogel was synthesized for local gene transfer in the heart. Initially, the luciferase gene was delivered into mouse heart. The intensity of gene expression assessed by optical imaging was closely correlated with the expressed protein concentration measured by luciferase assay in homogenized heart. Polymeric hydrogel-based gene transfer enhanced gene expression up to 4 fold, compared with naked plasmid, and displayed 2 bi-modal expression profiles with peaks at 2 days and around 25 days after local injection. Histological analyses showed that gene expression was initially highest in the myocardium, whereas lower and longer expression was seen mainly in fibrotic or inflammatory cells that infiltrated the injury site during injection. Next, a rat myocardial infarction model was made for 1 week, and human vascular endothelial growth factor (hVEGF) plasmid was injected into the infarct area with an amphiphilic thermo-responsive polymer. Enhanced and sustained hVEGF expression in the infarct region mediated by amphiphilic thermo-responsive polymer increased capillary density and larger vessel formation, thus enabling effective angiogenesis.
Kwon
Jin Sook
JS
Department of Cardiology, Chonnam National University Medical School, The Brain Korea 21 Project, Centre for Biomedical Human Resources at Chonnam National University, Gwangju 501-746, Republic of Korea.
Park
In Kyu
IK
Cho
Ae Shin
AS
Shin
Sun Mi
SM
Hong
Moon Hwa
MH
Jeong
Seo Yeon
SY
Kim
Yong Sook
YS
Min
Jung-Joon
JJ
Jeong
Myung Ho
MH
Kim
Won Jong
WJ
Jo
Seongbong
S
Pun
Suzie H
SH
Cho
Jeong Gwan
JG
Park
Jong Chun
JC
Kang
Jung Chaee
JC
Ahn
Youngkeun
Y
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D006801:Humans; D020100:Hydrogels; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010957:Plasmids; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D013501:Surface-Active Agents; D042461:Vascular Endothelial Growth Factor A; D008156:Luciferases