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Text
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URL Address
<a href="http://doi.org/10.1161/atvbaha.109.186445" target="_blank" rel="noreferrer noopener">http://doi.org/10.1161/atvbaha.109.186445</a>
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Pages
1817-1822
Issue
11
Volume
29
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Title
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Stimulation of Coronary Collateral Growth by Granulocyte Stimulating Factor Role of Reactive Oxygen Species
Publisher
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Arteriosclerosis Thrombosis and Vascular Biology
Date
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2009
2009-11
Subject
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ischemia; ROS; cardiomyocytes; receptor; Cardiovascular System & Cardiology; endothelial progenitor cells; expression; Hematology; activation; angiotensin-ii; neutrophils; neovascularization; bone-marrow; coronary collateral circulation; G-CSF; G-CSF
Creator
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Carrao A C R; Chilian W M; Yun J; Kolz C; Rocic P; Lehmann K; van den Wijngaard Jphm; van Horssen P; Spaan J A E; Ohanyan V; Pung Y F; Buschmann I
Description
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Objective-The purpose of this study was to determine whether G-CSF promotes coronary collateral growth (CCG) and decipher the mechanism for this stimulation. Methods and Results-In a rat model of repetitive episodic myocardial ischemia (RI, 40 seconds LAD occlusion every 20 minutes for 2 hours and 20 minutes, 3 times/d for 5 days) CCG was deduced from collateral-dependent flow (flow to LAD region during occlusion). After RI, G-CSF (100 mu g/kg/d) increased CCG (P < 0.01) (0.47 +/- 0.15) versus vehicle (0.14 +/- 0.06). Surprisingly, G-CSF treatment without RI increased CCG (0.57 +/- 0.18) equal to G-CSF + RI. We evaluated ROS by dihydroethidine (DHE) fluorescence (LV injection, 60 mu g/kg, during two episodes of ischemia). DHE fluorescence was double in G-CSF + RI versus vehicle + RI (P < 0.01), and even higher in G-CSF without RI (P < 0.01). Interestingly, the DHE signal did not colocalize with myeloperoxidase (immunostaining, neutrophil marker) but appeared in cardiac myocytes. The study of isolated cardiac myocytes revealed the cytokine stimulates ROS which elicit production of angiogenic factors. Apocynin inhibited G-CSF effects both in vivo and in vitro. Conclusions-G-CSF stimulates ROS production directly in cardiomyocytes, which plays a pivotal role in triggering adaptations of the heart to ischemia including growth of the coronary collaterals. (Arterioscler Thromb Vasc Biol. 2009; 29: 1817-1822.)
Identifier
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<a href="http://doi.org/10.1161/atvbaha.109.186445" target="_blank" rel="noreferrer noopener">10.1161/atvbaha.109.186445</a>
Format
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Journal Article or Conference Abstract Publication
2009
activation
angiotensin-ii
Arteriosclerosis Thrombosis and Vascular Biology
bone-marrow
Buschmann I
cardiomyocytes
Cardiovascular System & Cardiology
Carrao A C R
Chilian W M
coronary collateral circulation
endothelial progenitor cells
expression
G-CSF
Hematology
ischemia
Journal Article or Conference Abstract Publication
Kolz C
Lehmann K
Neovascularization
Neutrophils
Ohanyan V
Pung Y F
Receptor
Rocic P
ROS
Spaan J A E
van den Wijngaard Jphm
van Horssen P
Yun J