title: Attenuation of neointima formation following arterial injury in PAI-1 deficient mice.
abstract: Atherosclerosis is a chronic inflammatory disease in which the fibrinolytic system has been implicated as playing a major role. In order to directly assess the physiological impact an imbalanced fibrinolytic system has on both early and late stages of this disease, mice deficient for PAI-1 (PAI-1-/-) were used in a model of vascular injury/repair and compared to wildtype mice (WT). Copper-containing cuffs were placed around the carotid arteries of these mice and the injured arteries were removed at either 7 or 21 days for histological analyses. At both times after injury, fibrin was prevalent in WT arteries, whereas only diffuse in PAI-1-/- arteries. At 21 days after injury, a prominent, multilayered neointima was evident in WT arteries, with no evidence of a neointima in PAI-1-/- arteries. Results from this study directly confirm the involvement of the fibrinolytic system in vascular repair processes following injury and indicate that fibrin could potentially play a role in lesion formation by stimulating smooth muscle cell proliferation, collagen synthesis, and intracellular cholesterol accumulation.
authors.affiliation: W.M. Keck Center for Transgene Research, Notre Dame, Indiana, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Ploplis
authors.forename: F J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen