| Endothelial nitric oxide synthase overexpression provides a functionally relevant angiogenic switch in hibernating pig myocardium. | |
| | |
MedLine Citation:
|
PMID: 17418299 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVES: We investigated whether retroinfusion of liposomal endothelial nitric oxide synthase (eNOS) S1177D complementary deoxyribonucleic acid (cDNA) would affect neovascularization and function of the ischemic myocardium. BACKGROUND: Recently, we demonstrated the feasibility of liposomal eNOS cDNA transfection via retroinfusion in a model of acute myocardial ischemia/reperfusion. In the present study, we used this approach to target a phosphomimetic eNOS construct (eNOS S1177D) into chronic ischemic myocardium in a pig model of hibernation. METHODS: Pigs (n = 6/group) were subjected to percutaneous implantation of a reduction stent graft into the left anterior descending artery (LAD), inducing total occlusion within 28 days. At day 28, retroinfusion of saline solution containing liposomal green fluorescent protein or eNOS S1177D cDNA (1.5 mg/animal, 2 x 10 min) was performed. Furthermore, L-nitroarginine-methylester (L-NAME) was applied orally from day 28, where indicated. At day 28 and day 49, fluorescent microspheres were injected into the left atrium for perfusion analysis. Regional functional reserve (at atrial pacing 140/min) was assessed at day 49 by subendocardial segment shortening (SES) (sonomicrometry, percent of ramus circumflexus region). RESULTS: The eNOS S1177D overexpression increased endothelial cell proliferation as well as capillary and collateral growth at day 49. Concomitantly, eNOS S1177D overexpression enhanced regional myocardial perfusion from 62 +/- 4% (control) to 77 +/- 3% of circumflex coronary artery-perfused myocardium, unless L-NAME was co-applied (69 +/- 5%). Similarly, eNOS S1177D cDNA improved functional reserve of the LAD (33 +/- 5% vs. 7 +/- 3% of circumflex coronary artery-perfused myocardium), except for L-NAME coapplication (13 +/- 6%). CONCLUSIONS: Retroinfusion of eNOS S1177D cDNA induces neovascularization via endothelial cell proliferation and collateral growth. The resulting gain of perfusion enables an improved functional reserve of the hibernating myocardium. |
| | |
Authors:
|
Christian Kupatt; Rabea Hinkel; Marie-Luise von Brühl; Tilmann Pohl; Jan Horstkotte; Philip Raake; Chiraz El Aouni; Eckehard Thein; Stefanie Dimmeler; Olivier Feron; Peter Boekstegers |
Related Documents
:
|
10229739 - Lack of correlation between pattern of collateralization and misery perfusion in patien... 1151039 - The use of urokinase in acute myocardial infarction: report of two cases. 15023889 - Cd44 regulates arteriogenesis in mice and is differentially expressed in patients with ... 1529929 - Role of nitrates in acute myocardial infarction. 12433889 - Antiarrhythmic and anti-ischaemic effects of angina in patients with and without corona... 11514489 - Quantitative contrast echocardiographic assessment of collateral derived myocardial per... 15450109 - Adenosine a receptors are necessary for protection of the murine heart by remote, delay... 2385119 - Myocardial oxygen utilization after reversible global ischemia. 12669139 - Percutaneous angioplasty and stenting of left subclavian artery stenosis in patients wi... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-23 |
Journal Detail:
|
Title: Journal of the American College of Cardiology Volume: 49 ISSN: 1558-3597 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2007 Apr |
Date Detail:
|
Created Date: 2007-04-09 Completed Date: 2007-06-04 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
|
Languages: eng Pagination: 1575-84 Citation Subset: AIM; IM |
Affiliation:
|
Internal Medicine I, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. christian.kupatt@med.uni-muenchen.de |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Myocardial Stunning / enzymology* Neovascularization, Physiologic* Nitric Oxide Synthase Type III / biosynthesis* Swine |
| Chemical | |
Reg. No./Substance:
|
EC 1.14.13.39/Nitric Oxide Synthase Type III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopa...
Next Document: PCR examination of bronchoalveolar lavage samples is a useful tool in pre-clinical diagnosis of ovin...