Haemostasis Research Division

The Haemostasis Division performs research in the field of atherothrombosis in attempt to characterize its molecular pathomechanism culminating in cardiovascular and cerebrovascular diseases, which continue to be a major public health concern worldwide. The work in the division focuses on the enzymological evaluation of proteases involved in the dissolution of thrombi. A second area of interest is the interactions of blood vessel wall components and blood cells, which contribute to the formation and stabilization of intravascular thrombi. A major goal of the research is the identification of molecular targets, which allow development of thrombolytic strategies with higher efficiency than the therapeutic approaches available at present.

 

Members Press Releases
a
a
a
a
Molecular shield surrounding fibrin
a
a
White blood cells: guardians or foes of thrombi?
a
a
aa
a
a


a
a

aaBlood 2003; 101: 4380-4386 aaaalink
aaJ Biol Chem 2004; 279: 39863-39871 aaaalink
aaJ Thr Haemost 2007; 5: 1265-1273aaaa aaaalink
aaJ Thr Haem 2010; 8: 1624-1631aaaa aalinkaaaa
aaThr Res 2010; 126: e94-e101aaaa aalinkaaaa
a
a
a
a
The currently available clot-busting agents often fail to dissolve the blood-vessel plugs, which cause the tissue damage in heart attacks and strokes. The experimental and theoretical work accomplished in the Hemostasis Division has identified new structural components (proteins, lipids) derived from cells (platelets, white blood cells), which affect the efficiency of the dissolution process of the blood clots.
Details
a
a
Through our research we came to realise that white blood cells play a dual role in the progress of atherothrombosis. At first we noticed that they help to modify the structure of the blood vessel walls, enabling the formation of stable blood clots. This is obviously a negative attribute, however, the same blood cells subsequently have the ability to help dissolve the clots, so they are our friends and foes in equal measure.
Details
a
a
Mechanical stress and red blood cells are not passive bystanders in thrombolysis
a
a
Structural arsenal in the combat against fibrina
a
a
a
a
a
a
aaJ Thr Haem 2011; 9: 979-986 aaaalinkaaaa
aaA T V Biol 2011; 31: 2306- 13aaaa aaaalinka
aaBlood 2011; 117: 661-668aaaaaaaalink
a
a

a
a
The general notion is that mechanical forces and chemical reactions are two separate detached phenomena, but in thrombolysis the two are tightly coupled. We observed that in narrowing arteries the accelerated blood flow aligns the fibrin fibers along the axis of the shear forces and this mechanical effect profoundly increases the resistance of the clots to destruction by enzymes.
Details
a
a
a
In collaboration with the National Institute for Biological Standards and Control (London) and using genetic engineering techniques we produced module variants of the most specific endogenous clot-busting enzyme (tissue plasminogen activator, tPA). We approached the tPA structure/function relationships in fibrin of various architecture using recombinant domain-deleted and fluorescent protein-fusion tPA variants, with the help of which we could dissect the distinct roles of separate protein domains in different clot structures at different stages of their dissolution.
a

a