scholarly journals Gene transfer as a strategy to achieve permanent cardioprotection I: rAAV-mediated gene therapy with inducible nitric oxide synthase limits infarct size 1 year later without adverse functional consequences

2011 ◽  
Vol 106 (6) ◽  
pp. 1355-1366 ◽  
Author(s):  
Qianhong Li ◽  
Yiru Guo ◽  
Wen-Jian Wu ◽  
Qinghui Ou ◽  
Xiaoping Zhu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gene Therapy ◽  
Nitric Oxide Synthase ◽  
Gene Transfer ◽  
Infarct Size ◽  
Inducible Nitric Oxide Synthase ◽  
Functional Consequences ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Efficient inhibition of intimal hyperplasia by adenovirus-mediated inducible nitric oxide synthase gene transfer to rats and pigs in vivo

1998 ◽  
Vol 187 (3) ◽  
pp. 295-306 ◽  
Author(s):  
Larry L. Shears ◽  
Melina R. Kibbe ◽  
Alan D. Murdock ◽  
Timothy R. Billiar ◽  
Alena Lizonova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Gene Transfer ◽  
Inducible Nitric Oxide Synthase ◽  
Intimal Hyperplasia ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Gene Transfer of Inducible Nitric Oxide Synthase Impairs Relaxation in Human and Rabbit Cerebral Arteries

Stroke ◽  
2002 ◽  
Vol 33 (9) ◽  
pp. 2292-2296 ◽  
Author(s):  
C.A. Gunnett ◽  
D.D. Lund ◽  
M.A. Howard ◽  
Y. Chu ◽  
F.M. Faraci ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Gene Transfer ◽  
Inducible Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Preclinical Evaluation of Inducible Nitric Oxide Synthase Lipoplex Gene Therapy for Inhibition of Stent-Induced Vascular Neointimal Lesion Formation

2003 ◽  
Vol 14 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Andreas Muhs ◽  
Bernd Heublein ◽  
Jens Schletter ◽  
Andreas Herrmann ◽  
Manfred Rüdiger ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gene Therapy ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Lesion Formation ◽  
Preclinical Evaluation ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Cardioprotection Afforded by Inducible Nitric Oxide Synthase Gene Therapy Is Mediated by Cyclooxygenase-2 via a Nuclear Factor-κB–Dependent Pathway

Circulation ◽  
2007 ◽  
Vol 116 (14) ◽  
pp. 1577-1584 ◽  
Author(s):  
Qianhong Li ◽  
Yiru Guo ◽  
Wei Tan ◽  
Qinghui Ou ◽  
Wen-Jian Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gene Therapy ◽  
Gene Transfer ◽  
Infarct Size ◽  
Nuclear Factor ◽  
Wild Type ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Dependent Pathway ◽  
Inducible Nitric Oxide

Background— Gene therapy with inducible nitric oxide synthase (iNOS) markedly reduces myocardial infarct size; this effect is associated with cyclooxygenase-2 (COX-2) upregulation and is ablated by COX-2 inhibitors. However, pharmacological inhibitors are limited by relative lack of specificity; furthermore, the mechanism whereby iNOS gene therapy upregulates COX-2 remains unknown. Accordingly, we used genetically engineered mice to test the hypothesis that the cardioprotection afforded by iNOS gene transfer is mediated by COX-2 upregulation via a nuclear factor (NF)-κB–dependent pathway. Methods and Results— Mice received an intramyocardial injection of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 3 days later, myocardial infarction was produced by a 30-minute coronary occlusion followed by 4 hours of reperfusion. Among Av3/LacZ-treated mice, infarct size was similar in COX-2 −/− and wild-type groups. iNOS gene transfer (confirmed by iNOS immunoblotting and activity assays) markedly reduced infarct size in wild-type mice but failed to do so in COX-2 −/− mice. In transgenic mice with cardiac-specific expression of a dominant-negative mutant of IκBα (IκBα S32A,S36A ), the upregulation of phosphorylated IκBα, activation of NF-κB, and cardiac COX-2 protein expression 3 days after iNOS gene therapy were abrogated, which was associated with the abolishment of the cardioprotective effects afforded by iNOS gene therapy. Conclusions— These data provide strong genetic evidence that COX-2 is an obligatory downstream effector of iNOS-dependent cardioprotection and that NF-κB is a critical link between iNOS and COX-2. Thus, iNOS imparts its protective effects, at least in part, by recruiting NF-κB, leading to COX-2 upregulation. However, COX-2 does not play an important cardioprotective role under basal conditions (when iNOS is not upregulated).

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