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Reduction of endothelial dysfunction following VEGF gene therapy.

BACKGROUND/OBJECTIVES
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischaemic 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 upregulates eNOS. Therefore, we investigated coronary endothelium-dependent vasodilatation in patients before and after VEGF gene therapy.


METHODS
The effect of intracoronary acetylcholine infusion on coronary diameter was assessed at baseline and after three months of follow-up in patients with end-stage coronary artery disease treated with VEGF gene and in controls scheduled for elective PTCA (acetylcholine test at diagnostic angiography and before a subsequently scheduled PTCA).


RESULTS
Eight out of ten VEGF patients experienced a reduction in anginal symptoms. 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.


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.