Vascular endothelial growth factor is required for coronary collateral growth in the rat

Eiji Toyota, David C. Warltier, Tommy Brock, Erik Ritman, Christopher Kolz, Peter O'Malley, Petra Rocic, Marta Focardi, William M. Chilian

Research output: Contribution to journalArticle

103 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2108-2113
Number of pages6
JournalCirculation
Volume112
Issue number14
DOIs
StatePublished - Oct 4 2005

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Vascular Endothelial Growth Factor A
Growth
Coronary Occlusion
Vasodilation
Cardiac Arrhythmias
X-Ray Microtomography
Collateral Circulation
Dipyridamole
Microspheres
Myocardial Ischemia
Hemodynamics
Maintenance
X-Rays
Control Groups

Keywords

  • Angiogenesis
  • Collateral circulation
  • Coronary circulation
  • Growth substances

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Toyota, E., Warltier, D. C., Brock, T., Ritman, E., Kolz, C., O'Malley, P., ... Chilian, W. M. (2005). Vascular endothelial growth factor is required for coronary collateral growth in the rat. Circulation, 112(14), 2108-2113. https://doi.org/10.1161/CIRCULATIONAHA.104.526954

Vascular endothelial growth factor is required for coronary collateral growth in the rat. / Toyota, Eiji; Warltier, David C.; Brock, Tommy; Ritman, Erik; Kolz, Christopher; O'Malley, Peter; Rocic, Petra; Focardi, Marta; Chilian, William M.

In: Circulation, Vol. 112, No. 14, 04.10.2005, p. 2108-2113.

Research output: Contribution to journalArticle

Toyota, E, Warltier, DC, Brock, T, Ritman, E, Kolz, C, O'Malley, P, Rocic, P, Focardi, M & Chilian, WM 2005, 'Vascular endothelial growth factor is required for coronary collateral growth in the rat', Circulation, vol. 112, no. 14, pp. 2108-2113. https://doi.org/10.1161/CIRCULATIONAHA.104.526954
Toyota E, Warltier DC, Brock T, Ritman E, Kolz C, O'Malley P et al. Vascular endothelial growth factor is required for coronary collateral growth in the rat. Circulation. 2005 Oct 4;112(14):2108-2113. https://doi.org/10.1161/CIRCULATIONAHA.104.526954
Toyota, Eiji ; Warltier, David C. ; Brock, Tommy ; Ritman, Erik ; Kolz, Christopher ; O'Malley, Peter ; Rocic, Petra ; Focardi, Marta ; Chilian, William M. / Vascular endothelial growth factor is required for coronary collateral growth in the rat. In: Circulation. 2005 ; Vol. 112, No. 14. pp. 2108-2113.
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AU - Warltier, David C.

AU - Brock, Tommy

AU - Ritman, Erik

AU - Kolz, Christopher

AU - O'Malley, Peter

AU - Rocic, Petra

AU - Focardi, Marta

AU - Chilian, William M.

PY - 2005/10/4

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N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Collateral circulation

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