title: Alpha(2)-antiplasmin gene deficiency in mice does not affect neointima formation after vascular injury.
abstract: The hypothesis that alpha(2)-antiplasmin (alpha(2)-AP), the main physiological plasmin inhibitor, plays a role in neointima formation was tested with use of a vascular injury model in wild-type (alpha(2)-AP(+/+)) and alpha(2)-AP-deficient (alpha(2)-AP(-/-)) mice. The neointimal and medial areas were similar 1 to 3 weeks after electric injury of the femoral artery in alpha(2)-AP(+/+) and alpha(2)-AP(-/-) mice, resulting in comparable intima/media ratios (eg, 0.43+/-0.12 and 0.42+/-0.11 2 weeks after injury). Nuclear cell counts in cross-sectional areas of the intima of the injured region were also comparable in arteries from alpha(2)-AP(+/+) and alpha(2)-AP(-/-) mice (78+/-19 and 69+/-8). Fibrin deposition was not significantly different in arteries of both genotypes 1 day after injury, and no mural thrombosis was detected 1 week after injury. Fibrinolytic activity in femoral arterial sections, as monitored by fibrin zymography, was higher in alpha(2)-AP(-/-) mice 1 week after injury (P<0.001) but was comparable in both genotypes 2 and 3 weeks after injury. Staining for elastin did not reveal significant degradation of the internal elastica lamina in either genotype. Immunocytochemical analysis revealed a comparable distribution pattern of alpha-actin-positive smooth muscle cells in both genotypes. These findings indicate that the endogenous fibrinolytic system of alpha(2)-AP(+/+) mice is capable of preventing fibrin deposition after vascular injury and suggest that alpha(2)-AP does not play a major role in smooth muscle cell migration and neointima formation in vivo.
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium. roger.lijnen@med.kuleuven.ac.be
authors.forename: H R
authors.initials: HR
authors.lastname: Lijnen
authors.forename: B
authors.initials: B
authors.lastname: Van Hoef
authors.forename: M
authors.initials: M
authors.lastname: Dewerchin
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D004549:Elastin / Q000032:analysis / Q000378:metabolism; D004556:Electric Injuries; D005260:Female; D005263:Femoral Artery / Q000293:injuries* / Q000503:physiopathology*; D005337:Fibrin / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000979:alpha-2-Antiplasmin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D000199:Actins; D000979:alpha-2-Antiplasmin; D005337:Fibrin; D004549:Elastin