The neointimal hyperplasia effect of erythropoietin on carotid artery injury model of rat

Kim, Ki Hoon; Kweon, Kyoung Hee; Baek, Seung Hoon; Park, Byoung Hyun; Cho, Chung Gu

Abstract

BACKGROUN: Neointimal hyperplasia is major cause of instent restenosis in coronary artery and stenosis in arteriovenous fisula for hemodialysis. Erythropoietin is known to show proliferative effect on vascular smooth muscle cells in vitro study, but there is few in vivo study. This study investigated the effect of erythropoietin given subcutaneously to injured carotid arteries of rats on neointimal hyperplasia.
METHODS
Sprague-Dawley rat underwent common carotid artery (CCA) balloon injury. Erythropoietin was given subcutaneously to balloon-injured rats (n=6) in 100 U/Kg/week by dividing three times. The control group (n=6) was treated with normal saline only. Two weeks later, the lumen and the neointimal area were obtained and compaired. Actively proliferating cells of neointimal area were observed by microscopy using PCNA staining method.
RESULTS
Luminal area was 0.233 +/- 0.073 mm2, 0.112 +/- 0.047 mm2 in the control and the erythropoietin treated group respectively. The area was significantly smaller in the treatment group (p<0.05). Neointimal area and neointimal area/medial area ratio were 0.148 +/- 0.029 mm2, 0.226 +/- 0.056 mm2 and 1.169 +/- 0.146 min, 1.953 +/- 0.465 min in the control and the erythropoietin treated group respectively (p<0.05), but no significant difference was observed in medial area between the control and the erythropoietin treated group. Actively proliferating cells of neointimal area were more commonly observed in erythropoietin treated group.
CONCLUSION
Erythropoietin increases neointimal cell proliferation in the rat carotid artery injury model. So, erythropoietin treatment may contributes to the development of arteriovenous fistula stenosis caused by neointimal hyperplasia but, further studies are required to elucidate the mechanism and the effect of erythropoietin at various time and dose in neointimal hyperplasia.