Functional characteristics of coronary vasomotor function following intramyocardial gene therapy with naked DNA encoding for vascular endothelial growth factor165.
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischemic myocardium in experimental models and possibly in patients with end-stage coronary artery disease. In addition to its proliferative and migratory effect on endothelial cells, it also activates and up-regulates endothelial nitric oxide synthase (eNOS). Therefore, the authors investigated coronary endothelium-dependent vasodilatation in patients before and after VEGF gene therapy. The effect of intracoronary acetylcholine infusion on coronary diameter was assessed at baseline and after 3 months follow-up in patients with end-stage coronary artery disease treated with VEGF gene and in controls scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) (acetylcholine test at diagnostic angiography and before a subsequently scheduled PTCA). Five out of six VEGF patients experienced a reduction in anginal complaints. Angiographic evidence for improved collateral filling was evident in two out of six patients. The vasoconstrictive response to acetylcholine was partly converted into dilatation. In contrast, the acetylcholine response in control patients remained vasoconstrictive. In conclusion, VEGF gene therapy has an important beneficial effect on the functional characteristics of the myocardial vascular network. Therefore, this therapy can potentially play an important role in all stages of the atherosclerotic process.
Tio
Ren A
RA
Department of Cardiology, Thoraxcentre, University Hospital Groningen, The Netherlands. r.a.tio@thorax.umcg.nl
Wijpkema
Jasper S
JS
Tan
Eng S
ES
Asselbergs
Folkert W
FW
Hospers
Geke A P
GA
Jessurun
Gillian A J
GA
Zijlstra
Felix
F
D000109:Acetylcholine / Q000008:administration & dosage; D000368:Aged; D000800:Angioplasty, Balloon / Q000379:methods; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D015425:Myocardial Reperfusion / Q000379:methods; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D004247:DNA; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine