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Novel findings about neovessel formation

The formation of blood vessels is a normal process during embryogenesis and wound healing. But there is also an unwanted formation of blood vessels, in tumors, for example, or in retinopathy, an eye disease that affects many diabetics. Researcher Mattias Belting at Lund University, together with an American research team at The Scripps Research Institute, has uncovered previously unknown mechanisms behind the generation of blood vessels that may pave the way for new drugs in the future.

The main role in the new findings is played by a protein called tissue factor. This factor turns out to have both a stimulatory function and an inhibitory function in the generation of blood vessels. Normally these two functions neutralize each other, but in diseases like retinopathy - where unwanted blood vessels grow into the retina - this balance is disturbed. The research team shows this in an article in the May issue of Nature Medicine.

Tissue factor is found in the cell walls of endothelial cells that line the lumenal side of blood vessels. The part of the tissue factor that faces the cell exterior sends signals, in combination with a certain so-called coagulation factor, to activate blood vessel cells to generate new vessel structures. The part of the tissue factor that resides on the inside of cells sends opposing signals that inhibit cell activation.

The group has unraveled these mechanisms by using several methods. For one thing, they have managed to generate transgenic mice that lack either the inhibitory mechanism, the stimulatory mechanism, or both. The results turned out accordingly: in mice without the inhibitory mechanism, for example, they have observed abnormally rapid growth of blood vessels in the retina and in tumors.

Another discovery reported in the article involves pathologically altered blood vessels from deceased patients with diabetes retinopathy. In these vessels it could be seen that the stimulatory mech
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Contact: Mattias Belting
mattias.belting@medkem.lu.se
46-46-222-4077
Swedish Research Council
10-May-2004


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