Augmented arterial wall expression of type-1 plasminogen activator inhibitor induced by thrombosis.
Type-1 plasminogen activator inhibitor (PAI-1), the primary physiological inhibitor of endogenous plasminogen activators, modulates fibrinolysis, cell migration, and tissue repair. To determine whether genetic expression of PAI-1 is augmented in the walls of vessels exposed to thrombi but not to a direct physical insult such as electrical injury, we induced arterial thrombosis in rabbit carotid arteries with intraluminal surgical silk sutures and performed in situ hybridization for PAI-1 messenger RNA (mRNA) and immunohistochemistry for PAI-1 antigen at selected intervals. PAI-1 activity in plasma remained virtually constant. In contrast, PAI-1 mRNA increased in endothelial cells juxtaposed to thrombi, in smooth muscle cells adjacent to the neointima, and in macrophages surrounding the suture material. PAI-1 protein was detected in regions in which PAI-1 mRNA was expressed. The increased expression of PAI-1 mRNA colocalized with PAI-1 protein in the endothelium juxtaposed to thrombi may potentiate thrombosis by shifting the local balance between fibrinolysis and thrombosis toward thrombosis. Furthermore, it may alter vascular remodeling and predispose to stenosis after interventions such as angioplasty, in which local thrombosis cannot be avoided.
Sawa
H
H
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
Fujii
S
S
Sobel
B E
BE
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D013927:Thrombosis / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger