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VEGF 165 transfection decreases postischemic NF‐κB‐dependent myocardial reperfusion injury in vivo: role of eNOS phosphorylation
Author(s) -
Kupatt Christian,
Hinkel Rabea,
Vachenauer Robert,
Horstkotte Jan,
Raake Philip,
Sandner Torleif,
Kreuzpointner Robert,
Müller Fabian,
Dimmeler Stefanie,
Feron Olivier,
Boekstegers Peter
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0673fje
Subject(s) - enos , nitric oxide , medicine , nitric oxide synthase , transfection , reperfusion injury , endocrinology , ischemia , phosphorylation , vascular endothelial growth factor , chemistry , vegf receptors , biochemistry , gene
Endothelial nitric oxide synthase (eNOS) phosphorylation increases nitric oxide formation, for example, after VEGF stimulation. We investigated whether nitric oxide formed after overexpression of VEGF or of phosphomimetic eNOS (S1177D) affects PMN‐induced myocardial detriment after ischemia and reperfusion. Pigs ( n =8 per group) were subjected to percutaneous liposome‐based gene transfer by retroinfusion of the anterior interventricular vein 48 h before LAD occlusion (60 min) and reperfusion (24 h). Thereafter, regional myocardial function was assessed as subendocardial segment shortening (SES), and infarct size was determined. Tissue from the infarct region, the noninfarcted area at risk, and a control region was analyzed for NF‐κB activation (EMSA), tumor necrosis factor (TNF)‐α, and E‐selectin mRNA and infiltration of polymorphonuclear neutrophils (PMN). L‐NAME was applied in one group of VEGF‐transfected animals. NF‐κB activition, PMN infiltration in the infarct region, and AAR were reduced after transfection of VEGF or eNOS S1177D, but not after VEGF+L‐NAME coapplication. Infarct size decreased, whereas SES improved after either VEGF or eNOS S1177D transfection, an effect inhibited by L‐NAME coapplication. Retroinfusion of liposomal VEGF cDNA reduces NF‐κB‐dependent postischemic inflammation and subsequent myocardial reperfusion injury, an effect mediated at least in part by enhanced eNOS phosphorylation.