Erythropoietin Enhances Arterioles More Significantly Than it Does Capillaries in an Infarcted Rat Heart Model

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Erythropoietin (Epo) is a hormone which regulates erythrocyte production. It has recently become known that Epo enhances angiogenesis. However, since shear stress is an initiator of arteriogenesis, this increase with Epo may be due to increased shear stress from erythrocytosis. To clarify this, we compared the effects of Epo on both angiogenesis and arteriogenesis. Myocardial infarction was induced by LAD ligation in Wistar rats (Epo, G-CSF and control). Epo (1,000 IU/kg) was administered immediately after ligation of the LAD. G-CSF was administered at 100 μg/kg/day for 5 days after the coronary ligation. Four weeks later, coronary angiography was performed using synchrotron radiation coronary micro-angiography with a Langendorff apparatus. The number of vessels was investigated by microscopy. The numbers of capillaries and arterioles (> 100 μm in diameter) were measured. Microscopical examination: Capillary density in the twilight zone was 95 ± 19 in the control group, 126 ± 24 in the G-CSF group, and 142 ± 32 in the EPO group (control versus Epo: P < 0.005, control versus G-CSF: P < 0.05). Arteriole numbers were 4.3 ± 0.2 in the control group, 6.9 ± 1.0 in the G-CSF, and 11.8 ± 0.6 in the Epo group (control versus Epo: P < 0.00001, G-CSF versus Epo: P < 0.00001, control versus G-CSF: P < 0.00001). The ratios of arterioles and capillaries were 0.048 ± 0.013 in the control group, 0.057 ± 0.016 in the G-CSF group, and 0.088 ± 0.019 in the Epo group (control versus Epo: P < 0.0005, G-CSF versus Epo: P < 0.05). Angiography: The number of crossing arterioles in the 2 mm lattice was 5.4 ± 1.7 in the Epo group and 3.8 +/-0.4 in the control group (P < 0.05). The gray scale values for the evaluation of capillaries was 128 ± 3.7 and 119 ± 2.1 in the Epo and control groups, respectively (P < 0.00005). Epo enhanced arterioles more significantly than it did capillaries in this infarcted rat heart model.



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