Restoration of blood flow and evaluation of corresponding angiogenic events by scanning electron microscopy after a single dose of VEGF in a model of peripheral vascular disease

被引:13
作者
Kofidis T. [1 ,3 ]
Nolte D. [1 ]
Simon A.R. [1 ]
Metzakis A. [1 ]
Balsam L. [2 ]
Robbins R. [2 ]
Haverich A. [1 ]
机构
[1] Div. of Thoracic Surgery, Hannover Medical School, Hannover
[2] Cardiothoracic Surgery Department, Falk Research Center, Stanford Medical School, Stanford
[3] Department of Cardiothoracic Surgery, Falk Cardiovascular Research Center, Stanford Medical School, Stanford, CA 94305-5247
关键词
Collaterals; Growth factors; Hind limb ischemia; Microcirculation; Scanning electron microscopy;
D O I
10.1023/A:1021561507227
中图分类号
学科分类号
摘要
The angiogenic effect of vascular endothelial growth factor (VEGF) has typically been assessed by indirect methods, including microsphere injection and angiography. Here, we use 3-D scanning electron microscopy (SEM) to directly visualize patterns of angiogenesis after a single bolus administration of VEGF in a model of peripheral vascular ischemia. Hind limb ischemia was induced by subcutaneous turniquet implantation in adult Wistar rats. The control group (group A, n = 10) was left untreated, group B (n = 10) received a single dose of VEGF (50 μg) injected in the peroneus muscle. LASER Doppler was applied for blood flow measurements. Animals were sacrificed on day 14 after ischemia induction and vascular casting was performed. Angiogenetic events such as 'tiny lateral sprouts', 'arcus formations', confluences and the angle of sprouting were assessed by SEM. Significant capillary sprouting was observed in both groups. VEGF-treated limbs demonstrated higher degrees of capillary growth (P = 0.01) and flow recovery (P = 0.028). 3-D-SEM showed sprouts to be more frequent in group B. Tiny lateral sprouts, which always left the mother vessel at an angle of 90° and which were of small diameter and lacked imprints of endothelial cell nuclei, were more frequent in the VEGF-treated group (P = 0.018). Arcus formation was significantly higher in the treated group (P = 0.02). We have developed a simple and effective experimental model of ischemia. For the study of angiogenic phenomena, 3-D imaging of the microvasculature offers a direct and conclusive method for the study of angiogenic events.
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页码:87 / 92
页数:5
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