title: Angiotensin II infusion induces site-specific intra-laminar hemorrhage in macrophage colony-stimulating factor-deficient mice.
abstract: Angiotensin II (AngII) infusion promotes macrophage infiltration into the aortic wall resulting in several forms of vascular pathology. To determine the causal role of macrophages in these vascular diseases, we used osteopetrotic (op) male mice in which a natural mutation ablates production of M-CSF and results in severe depletion of monocytes. AngII infusion into apoE-/- mice resulted in increased atherosclerosis that was attenuated in op mice. AngII infusion in op mice unexpectedly produced grossly discernable thickening of the proximal thoracic aorta characterized by intra-mural hematoma. This pathology was also observed in apoE+/+ x op male mice, and therefore, independent of hyper-lipidemia. No perceptible structural properties of aortas from op mice could be discerned prior to AngII infusion. Regional effects in the contractile response to phenylephrine were noted in aortic rings with enhanced responsivity in the upper thoracic aortas of op mice compared to those from +/+ mice. No differences in contractile response were noted in aortic rings from the lower thorax. In conclusion, deficiency of M-CSF attenuated AngII-induced atherosclerosis but led to an unanticipated pathology of intra-laminar hemorrhage in the upper aortic regions.
authors.affiliation: Cardiovascular Research Center, Wethington Building, Room 521, University of Kentucky, Lexington, KY 40536-0200, USA.
authors.forename: Fjoralba
authors.initials: F
authors.lastname: Babamusta
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Moorleghen
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.forename: Xiang-An
authors.initials: XA
authors.lastname: Li
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage* / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D005260:Female; D016368:Frameshift Mutation; D006406:Hematoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D006470:Hemorrhage / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D015918:Infusion Pumps, Implantable; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism
chemical_list: D000804:Angiotensin II; D016173:Macrophage Colony-Stimulating Factor