Impaired arterial neointima formation in mice with disruption of the plasminogen gene.

Carmeliet, Peter; Moons, Lieve; Ploplis, Victoria A.; Plow, Edward F.; Collen, Désiré

doi:10.1172/jci119148

Cited by 191 publications

(151 citation statements)

References 38 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…The absence of plasmin activity results in the formation of the fibrin-rich viscous or membranous material typically seen in patients with ligneous conjunctivitis and in mice with targeted disruption of the plasminogen gene. 19,20,31 An inflammatory reaction combined with activation of inflammatory cells and fibroblasts, with a drying out of the fibrin, results in the wood-like appearance of the conjunctival lesions. In a double-gene knockout-mouse model, the combination of plasminogen deficiency and fibrinogen deficiency prevents corneal fibrin deposits and associated inflammatory reactions and restores normal wound healing.…”

Section: Discussionmentioning

confidence: 99%

Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

Schött

Dempfle²,

Beck³

et al. 1998

N Engl J Med

145

114

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

Schött

Dempfle²,

Beck³

et al. 1998

N Engl J Med

145

114

View full text Add to dashboard Cite

“…Studies using gene knockout mice have shown that plasminogen deficiency impairs and PAI-1 deficiency enhances neointimal development after arterial injury. 56,57 These changes in neointimal formation may reflect an important role of plasmin-mediated proteolysis of the ECM in releasing constraints that interfere with VSMC migration. In addition, PAI-1 can also directly impair VSMC migration by binding to vitronectin and thereby interfere with its interactions with the cellular vitronectin receptor ␣V␤3 that facilitates integrin-mediated cell migration.…”

Section: Discussionmentioning

confidence: 99%

Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells

Bouchie

Hansen

Feener

1998

ATVB

105

View full text Add to dashboard Cite

Abstract-Increased expression of plasminogen activator inhibitor-1 (PAI-1) has been reported in atherosclerotic and balloon-injured vessels. Little is known regarding the factors and mechanisms that may negatively regulate PAI-1 expression. In this report, the effect of cGMP-coupled vasoactive hormones, including natriuretic factors and nitric oxide, on the regulation of PAI-1 expression in vascular smooth muscle cells was examined. Atrial natriuretic factor 1-28 (ANF) and C-type natriuretic factor-22 (CNP) reduced angiotensin II (Ang II)-and platelet-derived growth factor-stimulated PAI-1 mRNA expression in rat aortic smooth muscle cells by 50% to 70%, with corresponding reductions in PAI-1 protein release. Treatment of human aortic smooth muscle cells with CNP similarly inhibited both platelet-derived growth factor-induced PAI-1 mRNA expression and PAI-1 protein release by 50%. Dose-response studies revealed that the inhibitory effects of CNP and ANF on PAI-1 expression were concentration dependent, with IC 50 s of Ϸ1 nmol/L for both natriuretic peptides. Ang II-stimulated PAI-1 expression was also inhibited by the nitric oxide donor S-nitroso-N-acetylpenicillamine.

show abstract

“…Because of the variable number of invasive sprouts and the different amounts of tumor mass in the different specimens, we measured the maximum depth of individual tumoral sprouts and calculated the average distance of penetration using the Quantimet 600 imaging 36 (Leica, Van Hopplynus, Brussels, Belgium).…”

Section: Methodsmentioning

confidence: 99%

Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization

Bajou

Noël

Gerard

et al. 1998

Nat Med

623

474

View full text Add to dashboard Cite

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angio-genesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis.Tumor cell invasion and metastatic processes require the coordinated and temporal regulation of a series of adhesive, proteolytic and migratory events 1 . The plasminogen activator (PA)-plasmin proteolytic system has been implicated in these processes. Urokinase-type (uPA) and tissue-type (tPA) plasminogen activators are serine proteases that catalyze the conversion of inactive plasminogen into plasmin, a broadly acting enzyme able to degrade a variety of extracellular matrix proteins and to activate metalloproteinases and growth factors 2,3 . Plasminogen and uPA bind to their specific receptors directing plasmin activity to the migrating tumor cell surface. The activities of PA are directly controlled by specific inhibitors, the PA inhibitors 1 and 2 (PAI1 and PAI2) (ref. 4).Many studies have focused on the role of uPA in cellular invasion and metastasis. Much of the data supporting the role of uPA in these events derives from in vitro and in vivo experiments demonstrating a correlation between uPA expression and cell invasion and metastasis as well as reduction of metastatic potential by using natural or synthetic serine protease inhibitors, neutralizing antibodies to uPA or antisense oligonucleotides 5,6 . PAI1 may also be directly involved in cancer progression. Both tumor cells and capillary endothelial cells express higher levels of PAI1 than other cell types [7][8][9] . Surprisingly, this inhibitor is necessary for optimal invasion of cultured lung cancer cells 10 , and an increasing number of clinical studies have demonstrated that high PAI1 levels indicate a poor prognosis for the survival of patients suffering from a variety of cancers [11][12][13] . However, as PAI1 is an acute-phase reactant 14 , it remains undetermined whether the increased PAI1 levels causally contribute to, or rather are the consequence of, the malignancy.Various observations indicate that the PA system may provide both surface-associated protease activity and an adhesion mechanism for cells through interaction with vitronectin. Deng et al. suggested that the balance between cell adhesion and cell detachment is governed by PAI1 (ref. 15). The PAI1-mediated release of cells attached to vitronectin seems to occur independently of the abili...

show abstract

Impaired arterial neointima formation in mice with disruption of the plasminogen gene.

Abstract: To define the role of plasminogen (Plg) in the smooth muscle cell response after arterial wall injury, neointima formation was evaluated after electric injury of the femoral artery in plasminogen-deficient (Plg

Cited by 191 publications

References 38 publications

Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells

Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization

Contact Info

Product

Resources

About