1. ¹Prenatal Gene Therapy Group, Institute for Women's Health, Royal Free and University College London Medical School, London, UK
2. ²Division of Medicine, Centre for Cardiovascular Biology and Medicine, BHF Laboratories, Royal Free and University College London Medical School, London, UK
3. ³Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London, UK
4. ⁴Department of Pathology, Imperial College School of Medicine, London, UK
5. ⁵Biological Services Unit, Royal Veterinary College, London, UK

Correspondence: Dr AL David, Department of Obstetrics and Gynaecology, Institute for Women's Health, UCL, 86–96 Chenies Mews, University College London, London WC1E 6HX, UK. E-mail: a.david@ucl.ac.uk

⁶These authors contributed equally to this work.

Received 28 November 2007; Revised 25 March 2008; Accepted 28 April 2008; Published online 19 June 2008.

Abstract

Impaired materno-placental perfusion causes two important obstetric complications, fetal growth restriction and preeclampsia. This study investigated whether adenoviral vector-mediated overexpression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtAs) increases uterine artery blood flow (UBF). First-generation adenovirus vectors (5 10¹¹ particles) containing the VEGF gene (Ad.VEGF-A or -D) or the -galactosidase reporter gene (Ad.lacZ) were injected into the UtAs of pregnant sheep (n=6) at 88–102 days of gestation (term=145 days). UBF was measured using Doppler sonography before, and 4–7 days after injection. Mean UBF increased significantly from 233156 (s.d.) ml min^-1 to 753415 ml min^-1 following Ad.VEGF-A injection (P=0.005, n=5); Ad.lacZ infection had no significant effect. Organ bath experiments on uterine arterial sections 4–7 days after injection showed that, compared with Ad.lacZ vessels, Ad.VEGF-A-transduced vessels had a reduced contractile response to phenylephrine (E_max 14810.9 vs E_max 228.227.5, P<0.05) but increased relaxation with bradykinin (pD2 (-log EC₅₀) values 9.110.01 vs 8.650.11, P<0.05). Injection of Ad.VEGF-A into the UtAs increases UBF by enhancing vasodilatation. This may provide the basis for therapy in pregnancies complicated by uteroplacental insufficiency.