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Effects of vascular endothelial growth factor (VEGF) A and VEGF B gene transfer on vascular reserve in a conscious rabbit hindlimb ischaemia model
Author(s) -
Wright Christine E
Publication year - 2002
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2002.03773.x
Subject(s) - arteriogenesis , hyperaemia , vascular endothelial growth factor , medicine , hindlimb , ischemia , angiogenesis , vascular endothelial growth factor a , cardiology , blood flow , vegf receptors
Summary 1. As a result of the ageing population, there are increasing numbers of patients with severe peripheral vascular occlusive disease associated with intermittent claudication (pain on walking) and decreased exercise tolerance. There is a great clinical need for pharmacological treatments that may stimulate collateral blood vessel growth, increase vascularity and improve skeletal muscle function. 2. Therapeutic angiogenesis using growth factors such as vascular endothelial growth factor (VEGF) has been used to improve collateral artery development in myocardial or skeletal muscle ischaemia. The broad aims of the work briefly summarized here were to compare the effects of VEGF A165 and VEGF B167 (500 µg, i.m., gene transfer) on calf blood pressure ratio and reactive hyperaemia in a chronic rabbit preparation with unilateral limb ischaemia. 3. Unilateral femoral artery ligation caused an immediate deficit (compared with the contralateral limb) of 72% in calf systolic blood pressure. There were improvements 14 days after ligation with VEGF A and VEGF B treatments compared with the vehicle control plasmid treatment, but a deficit remained of some 32%. 4. Reactive hyperaemic responses were significantly attenuated 7 days after ligation in the vehicle and VEGF A treatment groups. On day 14, this loss of vascular reserve was restored in the VEGF A group, but remained in the vehicle group (−30%). In VEGF B ‐treated animals, there was no deficit in reserve 7–14 days post‐ligation. 5. In conclusion, there is considerable value in the serial measurements of calf blood pressure ratio and reactive hyperaemia in the rabbit unilateral hindlimb ischaemia model. Gene transfer of either VEGF A or VEGF B allowed significant improvements in these indices compared with vehicle but, at 14 days post‐ligation, large deficits still remained. Studies extending this experimental period are in progress.