Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 559

9.8.3 Embolus Extravasation

Small clots that form in blood vessels can be removed by hemodynamic forces
and fibrinolysis. A third mechanism relies on endothelial cells that emit membrane
projections that envelop emboli and carry them into the perivascular tissue [ 1028 ].
Embolus extravasation occurs within 2 to 7 days especially in the cerebral vascula-
ture to avoid prolonged microvascular occlusion and relatively quickly recanalize
microvessels. This process creates a breach in the blood-brain barrier. The rate of
embolus translocation decays when activity of matrix metallopeptidases MMP2 and
MMP9 is hindered.

9.8.4 Thrombosis

The vascular endothelium locally maintains blood flow, as it prevents blood
coagulation (thrombosis) and promotes fibrinolysis of any possible thrombus that
can incidentally appear. Endothelial cells lose their non-thrombogenic property
upon exposure to inflammatory stimuli (e.g., TNF

, and thrombin).
Transcription factor Kr uppel-like factor KLF2 140 regulates inflammatory
activation of endothelial cells and favors antithrombotic gene expression. Factor
KLF2: (1) provokes production of thrombomodulin, an inhibitor of blood
coagulation, and nitric oxide, an inhibitor of platelet aggregation, by NOS3; and
(2) favors fibrinolysis, as it lowers synthesis of plasminogen activator inhibitor-1
and promotes tissue plasminogen activator; and (3) precludes cytokine-mediated
induction of tissue factor [ 1029 ].
Thrombi are formed in blood vessels and cardiac cavities from clotting factors
using the same procedure as coagulation. The contact between blood and an unusual
material triggers the clotting reaction cascade quickly (in few seconds), activating
platelets that adhere to the endothelial gap. Mural thrombi are dominantly composed
of platelets. Platelets bind fibrinogen that forms fibrin strands, which are cofactors
in platelet aggregation. Tissue factor and plasma fibronectin are also involved in
thrombus growth.
When the blood flow is high enough, the microthrombi do not strongly adhere to
the wall and can be destroyed by the fibrinolytic system. When the blood flow is low,
the competition between activation and inhibition of coagulation favors thrombus
formation. A thrombus can develop and block the vessel lumen and then induce
ischemia of the irrigated tissues. Thrombus portions can detach; they are then carried
in the bloodstream as emboli (embolization). Emboli can block a vessel segment
downstream from the thrombus site. Local or remote blockades cause infarction of
the tissues normally irrigated by the corresponding blood vessels.

α ,IL1 β

140 A.k.a. lung Kruppel-like factor (LKLF).