Summary
The lysis of fibrin clots on the surface of cultured human omental tissue microvascular
endothelial cells (HOTMEC) and cultured human umbilical vein endothelial cells (HUVEC)
was studied. Fibrin clots were made by mixing fibrinogen, plasminogen and thrombin
on the surface of both cell types. Clot lysis was seen only on the surface of HOTMEC,
which were found to synthesize about 100-fold more tissue plasminogen activator (tPA)
antigen than HUVEC. Clot lysis of HOTMEC could be blocked by anti-tPA IgG but was
not affected by the incorporation of exogenous plasminogen activator (PAI) into the
clot in concentrations (75 arbitrary units) exceeding the tPA activity (21 ± 2.5 IU)
of the cells. Thus, it is likely that tPA secreted by HOTMEC is protected from inhibition
by PAI in the presence of fibrin and endothelial cells. The stimulation of EC to release
an excess of tPA over PAI, in contrast to the secretion of an excess of PAI over tPA
found in unstimulated cells in the absence of fibrin, is obviously no prerequisite
for the initiation of fibrinolysis on the surface of HOTMEC. As thrombin was used
for clot formation, its influence on tPA and PAI synthesis of both cell types was
investigated. In contrast to HOTMEC, which were not affected by Α-thrombin, HUVEC
revealed a dose-dependent increase in tPA and PAI synthesis upon incubation with the
enzyme. This increase in tPA production by HUVEC was not sufficient to lyse the clots
within 48 hours. Furthermore, HUVEC. behaved differently towards thrombin as these
cells in contrast to HOTMEC revealed the typical shape change reaction upon incubation
with the enzyme
Keywords
Endothelial cells - Clot lysis - Tissue plasminogen activator - Plasminogen activator
inhibitor
