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Adenovirus‐Mediated Gene Transfer of Angiopoietin‐1 Induces Angiogenesis in the Chronic Ischemic Myocardium
Author(s) -
Zhang Li,
Bapna Akanksha,
Shim Winston,
El Oakley Reida,
Lim Yean Teng,
Lim Tai Tian,
Teh Ming,
Ge Ruowen,
Sim Eugene
Publication year - 2002
Publication title -
journal of cardiac surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.428
H-Index - 58
eISSN - 1540-8191
pISSN - 0886-0440
DOI - 10.1046/j.1540-8191.2002.01014_1.x
Subject(s) - medicine , angiogenesis , ex vivo , revascularization , ischemia , neovascularization , collateral circulation , ventricle , angiopoietin , arteriogenesis , angiography , cardiology , in vivo , vascular endothelial growth factor , pathology , myocardial infarction , microbiology and biotechnology , vegf receptors , biology
Objective: Overexpression of Angiopoietin‐1 (Ang‐1), a newly identified angiogenic mediator, was shown to enhance angiogenesis in vitro, and augment collateral vessel development in animal model of limb ischemia. However, its potential effect on myocardium remains unclear. We tested the hypothesis that adenovirus‐mediated gene transfer of Ang‐1 (AdAng‐1) may stimulate revascularization in the ischemic myocardium. Methods: Ameroid constrictors were placed around the proximal left circumflex arteries of porcine hearts to induce chronic myocardial ischemia. Six weeks later, animals were randomized to three groups (ischemic control (without further interventions), AdNull (null adenoviral vector), and AdAng‐1). AdNull and AdAng‐1 were injected directly into the ischemic myocardium along the free wall of left ventricle, 10 9 pfu per injection, 10 injections per animal. Regional blood flow measurement was performed by fluorescence microspheres, in the AdAng‐1 group at the time of administration and 3 months later. Animals were then sacrificed. Collateral development was assessed by ex vivo angiography after treatment. Anti‐Factor VIII serum was applied to stain vascular endothelium, for quantifying the vascular density of treated areas. Results: Ex vivo angiography showed collateral formation in most of the animals. The average grade by quantitative assessment of angiograms in the AdAng‐1 group was higher, compared with the other two groups. Immunohistological studies ( Fig. 1) demonstrated that the average of vascular density of AdAng‐1 group was significantly higher than those of the other two groups. Most of the vessels developed were capillaries. The vector administration didn't cause additional inflammation in the myocardium. Conclusion: Administration of adenoviral vector coding for Ang‐1 might enhance angiogenesis, especially the formation of sustained collaterals in the ischemic myocardium.Figure 1.Immunohistochemistry (original magnification 200×) staining with anti‐Factor VIII for (A) ischemic control, (B) AdNull treated and (c) AdAng‐1 treated. Increased number of capillaries is demonstrated in the AdAng‐1 injection region.