GM-CSF deficiency delays neointima formation in a normolipidemic mouse model of endoluminal endothelial damage.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been implicated in atherogenesis and has been shown to have both pro- and antiatherogenic properties. Neointimal thickening is a prominent feature of early atherogenesis. This study aimed to examine the role of GM-CSF in neointimal formation induced by endothelial injury using a GM-CSF(-/-) mouse model. Neointimal thickening was induced by endothelial damage in the common iliac arteries of normolipidemic C57Bl/6 (wild-type) and GM-CSF(-/-) mice. Arteries were collected weekly for 3-7 weeks following surgery. A significant delay in neointimal formation in the GM-CSF(-/-) compared with wild-type mice was detected by morphometric analysis of the intimal area. Neointimal size was approximately 10% smaller in GM-CSF(-/-) mice at 4-6 weeks post-surgery, compared with wild-type mice. The neointima was composed predominantly of smooth muscle cells and there was no difference in the extent of endothelial cell coverage between the wild-type and GM-CSF(-/-) mice. Using immunohistochemistry, reduced macrophages (F4/80(+) cells), proliferating cells (proliferating cell nuclear antigen (PCNA)(+) cells) and platelet-derived growth factor-B were detected within the arteries of GM-CSF(-/-) mice compared with wild types at 4 weeks post-surgery. GM-CSF(-/-) mice had reduced connective tissue within the neointima compared with wild types at 5 weeks post-surgery, determined by trichrome staining. We conclude that GM-CSF deficiency reduces neointimal formation in a normolipidemic model, primarily due to reduced macrophage recruitment.
Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia.
Angie K
AK
Harris
Jie
J
Shen
Jane
J
Radford
Shisan
S
Bao
Brett D
BD
Hambly
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor