Endothelium in hemostasis and thrombosis

doi:10.1016/S0033-0620(97)80032-1

Progress in Cardiovascular Diseases

Volume 39, Issue 4, January–February 1997, Pages 343-350

https://doi.org/10.1016/S0033-0620(97)80032-1 Get rights and content

Endothelial cells synthesize and secrete PA and PAI, and thus provide anticoagulant and procoagulant regulatory mechanisms, respectively. Both plasminogen and plasminogen activators (t-PA and u-PA) bind to specific cellular receptors; assembly of components of the fibrinolytic system at the endothelial cell surface results in stimulation of fibrinolytic activity. Several mechanisms contribute to this stimulation, eg, enhanced plasminogen activation by t-PA or u-PA, enhanced conversion of scu-PA to tcu-PA, and impaired inhibition of plasmin by α₂-antiplasmin or of PAs by PAIs. Thus, the endothelial cell surface serves as a focal point for plasmin generation.

References (54)

CollenD et al.
Basic and clinical aspects of fibrinolysis and thrombolysis
Blood
(1991)
VassalliJ-D
The urokinase receptor
Fibrinolysis
(1994)
LijnenHR et al.
Congenital and acquired deficiencies of components of the fibrinolytic system and their relation to bleeding or thrombosis
Fibrinolysis
(1989)
AlessiMC et al.
Correlations between t-PA and PAI-1 antigen and activity and t-PA/PAI-1 complexes in plasma of control subjects and patients with increased t-PA or PAI-1 levels
Thromb Res
(1990)
KristensenP et al.
Human endothelial cells contain one type of plasminogen activator
FEBS Lett
(1984)
CamaniC et al.
The role of plasminogen activator inhibitor type 1 in the clearance of tissue-type plasminogen activator by rat hepatoma cells
J Biol Chem
(1994)
AndreasenPA et al.
Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes
FEBS Lett
(1994)
PatthyL
Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules
Cell
(1985)
MedcalfRL et al.
A DNA motif related to the cAMP-responsive element and an exon-located activator protein-2 binding site in the human tissue-type plasminogen activator gene promoter cooperate in basal expression and convey activation by phorbol ester and cAMP
J Biol Chem
(1990)
FujiwaraJ et al.
A novel regulatory sequence affecting the constitutive expression of tissue plasminogen activator (t-PA) gene in human melanoma (Bowes) cells
J Biol Chem
(1994)

ChandlerWL et al.

A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training

Blood

(1993)

ShatosMA et al.

Oxygen radicals generated during anoxia followed by reoxygenation reduce the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cell culture

J Biol Chem

(1990)

RacanelliAL et al.

Distribution and pharmacokinetics of active recombinant plasminogen activator inhibitor-1 in the rat and rabbit

Fibrinolysis

(1992)

HekmanCM et al.

Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants

J Biol Chem

(1985)

DeclerckPJ et al.

Purification and characterization of a plasminogen activator inhibitor-1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin)

J Biol Chem

(1988)

PreissnerKT et al.

Structural requirements for the extracellular interaction of plasminogen activator inhibitor 1 with endothelial cell matrix-associated vitronectin

J Biol Chem

(1990)

WesterhausenDR et al.

Multiple transforming growth factor-β-inducible elements regulate expression of the plasminogen activator inhibitor type-1 gene in Hep G2 cells

J Biol Chem

(1991)

FolloM et al.

Structure and expression of the human gene encoding plasminogen activator inhibitor, PAI-1

Gene

(1989)

LoskutoffDJ

Regulation of PAI-1 gene expression

Fibrinolysis

(1991)

BarnathanES et al.

Tissue-type plasminogen activator binding to human endothelial cells. Evidence for two distinct binding sites

J Biol Chem

(1988)

HajjarKA et al.

An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with Annexin II

J Biol Chem

(1994)

CesarmanGM et al.

An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation

J Biol Chem

(1994)

PlougM et al.

Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol

J Biol Chem

(1991)

BehrendtN et al.

The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

J Biol Chem

(1991)

EllisV et al.

Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor

J Biol Chem

(1991)

EllisV et al.

Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. Potentiation by U937 monocytes

J Biol Chem

(1989)

EllisV et al.

Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors

J Biol Chem

(1990)

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