Venous it is also involved in cellular adhesion,

Venous thromboembolism
(VTE) is characterised by clot formation within a vein resulting in reduced
blood flow, which in turn can lead to necrosis of localised tissue and organs (Yau, Teoh, & Verma, 2015). Any venous
circulation can be affected by thrombosis, and in VTE deep vein thrombosis
(DVT) and pulmonary embolism (PE) is included. The incidence in Europe ranges
from 104-183 per 100.000 person-years (Heit, 2015). In the United
states there is a yearly occurrence of 200.000 new cases (Kroegel &
Reissig, 2003).
There are several known risk factors for VTE including; age, active cancer,
major surgery, neurological disease with leg paresis, hospitalisation for acute
illness, nursing home confinement, trauma or fracture, pregnancy, oral
contraception, noncontraceptive oestrogen plus progestin, oestrogen, progestin,
BMI, urinary tract infection and prior superficial vein thrombosis (Heit, 2015). VTE is also
associated with a high rate of recurrence and reduced survival (Heit, 2015).

Development of venous
thrombosis is characterised by three key features (according to Virchow’s
triad): venous stasis, hypercoagulable states and vascular endothelium injury.
Venous stasis occurs when there is a hemodynamic imbalance which occurs in
regions with slow blood flow, the pooled blood will activate the coagulation
system resulting in a local hypercoagulability. This can lead to endothelial
damage which in turn leads to further activation of the homeostasis system.
Hypercoagulable states are formed when the balance between pro- and
anticoagulant is in favour of procoagulant. Injury to the vascular endothelium
causes changes in the clotting system which contributes to the
hypercoagulability. (Kroegel & Reissig, 2003)

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The endothelium
separates the blood from the surrounding tissue and serves many functions,
amongst them is to regulate the vascular tone and it is also involved in
cellular adhesion, vessel wall inflammation and smooth muscle cell
proliferation. Under normal conditions the endothelial surface prevents platelets
from attaching and thereby prevents thrombosis. This is done by production of
nitric oxide and prostaglandin I2. Occurrence of vascular injury causes
endothelial dysfunction whereby cellular and protein material can gather at the
site of injury, creating a blood clot. (Yau, Teoh, & Verma, 2015) Once the endothelium
becomes inflamed, a two-step process of activation is initiated. In the type I
activation (stimulation) leads to elevated levels of Ca2+ which
leads to increased blood flow and recruitment of leukocytes. Type II activation
is mediated by tumour-necrosis factor (TNF) and interleukin-1 (IL-1) which in
turn leads to an increase in blood flow, vascular leakage of plasma proteins
and recruitment of leukocytes. Thrombus formation is important in inflammation
since it by separating the infected tissue from healthy tissue, prevents the
microbes from spreading. (Pober & Sessa, 2007) The control of blood
coagulation is therefore important in development of VTE. (Yau, Teoh, & Verma, 2015)

The aim of
the project is to prioritize endothelial cell (EC)-genes that are associated
with venous thromboembolism for investigation and to perform assays to identify
the gene function and the relevance for VTE-development. This is done by firstly isolating and cultivating
Human Umbilical Vein Endothelial Cells (HUVEC), then the selected genes are
inhibited using RNAi. The gene function and role in growth, survival,
apoptosis, angiogenesis, inflammation and thrombosis/coagulation will be
studied using different assays. The working hypothesis is that the project will
lead to further knowledge of the role of EC in development of VTE and reveal
new, specific targets for pharmaceutical intervention.

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