title: Role of macrophage colony-stimulating factor in the development of neointimal thickening following arterial injury.
abstract: Evidence suggests that macrophage colony-stimulating factor (M-CSF) participates critically in atherosclerosis; little is known about the role of M-CSF in the development of neointimal hyperplasia following mechanical vascular injury. We examined the expression of M-CSF and its receptor, c-fms, in rodent and rabbit models of arterial injury. Injured rat carotid arteries expressed 3- to 10-fold higher levels of M-CSF and c-fms mRNA and protein following balloon injury as compared to uninjured arteries. In the rabbit, M-CSF protein expression was greatest in neointimal smooth muscle cells (SMCs) postinjury, with some expression in medial SMCs. M-CSF-positive SMCs exhibited markers of proliferation. At 30days postinjury, neointimal SMCs in the adjacent healed area near the border between injured and uninjured zone lost both proliferative activity and overexpression of M-CSF. The presence of induced M-CSF and c-fms expression correlated with the initiation of SMCs proliferation. M-CSF stimulated incorporation of [(3)H] thymidine in human aortic smooth muscle cells in a concentration-dependent manner. Serum-free conditioned medium from aortic SMCs also promoted DNA synthesis, and this effect was blocked by M-CSF specific antibody. To test further the role of M-CSF in vivo, we induced arterial injury by placing a periadventitial collar around the carotid arteries in compound mutant mice lacking apolipoprotein apoE (apoE(-/-)) and M-CSF. Loss of M-CSF abolished the neointimal hyperplastic response to arterial injury in apoE(-/-) mice. Local delivery of M-CSF to the injured artery restored neointimal proliferation, suggesting a critical role of M-CSF for the development of neointimal thickening following arterial injury.
authors.affiliation: Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
authors.forename: Satyesh K
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India; Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA; David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rajavashisth@ucla.edu.
authors.forename: Tripathi B
authors.initials: TB
authors.lastname: Rajavashisth
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015151:Immunoblotting; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D058426:Neointima / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016173:Macrophage Colony-Stimulating Factor
keywords: Balloon injury; Carotid artery; M-CSF; Neointimal proliferation; Smooth muscle cells; c-fms