Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice

Elastases degrade the extracellular matrix, releasing growth factors and ch emotactic peptides, inducing glycoproteins such as tenascin, and thereby pr omoting vascular cell proliferation and migration. Administration of serine elastase inhibitors reduces experimentally induced vascular disease. The a bility to mount an intrinsic anti-elastase response may, therefore, protect against intimal/medial thickening after vascular injury. To investigate th is, we showed that wire-induced endothelial denudation of the carotid arter y is associated with transient elevation in elastase activity and confirmed that this is abolished in transgenic mice overexpressing the serine elasta se inhibitor, elafin, targeted to the cardiovascular system. Ten days after injury, nontransgenic littermates show vessel enlargement, intimal thicken ing, increased medial area and cellularity, and 2-fold increase in tenascin . Injured vessels in transgenic mice become enlarged but are otherwise simi lar to sham-operated controls. Injury-induced vessel wall thickening, which is observed only in nontransgenic mice, is related to foci of neutrophils and macrophages, in addition to smooth muscle cells that fail to stain for a-actin and are likely dedifferentiated. Our study therefore suggests that a major determinant of the vascular response to injury is the early transie nt induction of serine elastase activity, which leads to cellular prolifera tion and inflammatory cell migration.