title: Decreased neointimal formation in Mac-1(-/-) mice reveals a role for inflammation in vascular repair after angioplasty.
abstract: Inflammation plays an essential role in the initiation and progression of atherosclerosis, but its role in vascular repair after mechanical arterial injury (i.e., percutaneous transluminal coronary angioplasty, PTCA) is unknown. In animal models of vascular injury, leukocytes are recruited as a precursor to intimal thickening. Furthermore, markers of leukocyte activation - in particular, increased expression of the beta2-integrin Mac-1 (alphaMbeta2, or CD11b/CD18), which is responsible for firm leukocyte adhesion to platelets and fibrinogen on denuded vessels - predict restenosis after PTCA. To determine whether Mac-1-mediated leukocyte recruitment is causally related to neointimal formation, we subjected mice lacking Mac-1 to a novel form of mechanical carotid artery dilation and complete endothelial denudation. We now report that the selective absence of Mac-1 impairs transplatelet leukocyte migration into the vessel wall, reducing leukocyte accumulation over time. Diminished medial leukocyte accumulation was accompanied by markedly reduced neointimal thickening after vascular injury. These data establish a role for inflammation in neointimal thickening and suggest that leukocyte recruitment to mechanically injured arteries may prevent restenosis.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. dsimon@rics.bwh.harvard.edu
authors.forename: D I
authors.initials: DI
authors.lastname: Simon
authors.forename: Z
authors.initials: Z
authors.lastname: Dhen
authors.forename: P
authors.initials: P
authors.lastname: Seifert
authors.forename: E R
authors.initials: ER
authors.lastname: Edelman
authors.forename: C M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: C
authors.initials: C
authors.lastname: Rogers
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology* / Q000503:physiopathology*; D017353:Gene Deletion; D007249:Inflammation / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008297:Male; D051379:Mice; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology
chemical_list: D016177:Macrophage-1 Antigen