Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart.
OBJECTIVE
The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart.


METHODS
To achieve the inducible expression of adeno-associated viral (AAV)-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element (HRE) sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry.


RESULTS
HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium.


CONCLUSIONS
The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.
Department of Rehabilitation Medicine of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Quan
Q
Wei
Xiao-lin
XL
Huang
Jing-yang
JY
Lin
Yu-jie
YJ
Fei
Zheng-xiang
ZX
Liu
Xin A
XA
Zhang
D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage* / Q000235:genetics; D015153:Blotting, Western; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics; D008297:Male; D055806:Microvessels / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D017202:Myocardial Ischemia / Q000473:pathology / Q000628:therapy*; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D060185:Tetraspanin 24
D015703:Antigens, CD; C554715:CD151 protein, human; C554717:Cd151 protein, rat; D051793:Hypoxia-Inducible Factor 1; D060185:Tetraspanin 24; D010751:Phosphopyruvate Hydratase
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