Vascular Endothelial Growth Factor Is Required for Coronary Collateral Growth in the Rat

Abstract

Background— The goal of this study was to determine whether the expression of vascular endothelial growth factor (VEGF) is critical for coronary collateral growth. Previous studies have provided an association between coronary collateral growth and VEGF, but none have allowed determination of a causal role. Methods and Results— We measured coronary collateral growth in rats subjected to repetitive episodes of myocardial ischemia (RI; one 40-second occlusion every 20 minutes for 2 hours 40 minutes, followed by 5 hours 20 minutes of rest, with this 8-hour cycle repeated 3 times per day for 10 days). Collateral growth was measured from blood flow (radioactive microspheres), visualization of arterial-arterial anastomoses (x-ray micro-CT), and maintenance of function during complete coronary occlusion in 3 groups of animals: sham (received instrumentation but no RI), experimental (subjected to RI), and anti–vascular endothelial growth factor (RI+anti-VEGF 0.6 mg/100 g per day) to block the endogenous actions of VEGF. In the 3 groups, native collateral flow (measurement for RI or sham protocol) averaged 0.2 to 0.3 mL · min −1 · g −1 of tissue. In the sham group, collateral flow did not increase during the protocol. Collateral flow in the control RI group increased by ≈6-fold to 1.63 mL · min −1 · g −1 tissue, but in the anti-VEGF group, collateral flow did not increase after the RI protocol (0.22 mL · min −1 · g −1 ). In acute experiments, collateral flow was unchanged during vasodilation with dipyridamole, indicating the increases in collateral flow are due to collateral growth and not vasodilation. X-ray micro-CT analysis revealed a 3-fold increase (versus sham group) in the number of arterial-arterial anastomoses per heart after RI, which was prevented by treatment with anti-VEGF. The growth of the collateral circulation was functional in the RI group because complete coronary occlusion did not induce any untoward effects on hemodynamics or arrhythmias. In the sham or anti-VEGF groups, coronary occlusion at the end of the protocol induced many arrhythmias and deterioration of function. Conclusions— From these results, we conclude that the expression of VEGF is critical to the growth of coronary collaterals.

Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gβγ

“…and W.M.C., unpublished observations, and ref. 23). The ischemic area of the left ventricle perfused by the LAD was isolated as ''ischemic area'' at day 3 and used to generate a cDNA library for screening in the yeast-based expression cloning system described above.…”

“…Repetitive transient myocardial ischemia. Repetitive transient myocardial ischemia was achieved in male Wistar rats (-315g) as described (23). Briefly, a pneumatic snare was implanted around the proximal left anterior descending artery (LAD) under isoflurane anesthesia.…”

The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: new target molecules for pharmacotherapy

“…Кроме первостепенной роли в ангиогенезе, VEGF-A также вовлечён в целый ряд других процессов в центральной нервной системе, таких как: онтогенетическое развитие клеток нервной системы, включая процессы миграции, дифференцировки, синаптогенеза и миелинизации [22]; нейропротекция [23][24][25][26]; стимуляция нейрогенеза в зрелом возрасте [27][28][29][30]; постишемическое восстановление ткани головного мозга [14,31] и сосудов [32][33][34], стимуляция гиппокамп-зависимых механизмов формирования памяти [35]. VEGF-A также принимает участие в таких патологических процессах, как атерогенез [36,37] и формирование отёка головного мозга [2,[38][39][40][41][42].…”

Design study of compact Laser-Electron X-ray Generator for material and life sciences applications

“…This SRM imaging system was used to evaluate morphometric and physiological evaluation of coronary collateral microvessels development in stem cells transplantation in rats. The 6 μm resolution images were first obtained on beating hearts that was not previously available for conventional angiography as well as for micro CT. For example, coronary collateral growth was studied earlier by micro CT, but with spatial resolution three times larger -18 μm, and as was discussed in section 4 this could be performed only at postmortem examination [33] with long enough exposures. Now efforts are being done to improve the system in two respects: (a) to reduce the exposure time down to 0.1 ms in order to obtain blur-free images and completely use the resolving potential of the detector (b) to switch from ex-vivo to in-vivo experiments with individual animals.…”