British Society for Haematology. Listening. Learning. Leading British Society for Haematology. Listening. Learning. Leading
04 July 2018

Scientists are developing a new approach to inhibiting the blood vessel leakiness that can lead to septic shock.

Several diseases raise the risk of vascular leakage through permeable capillaries, including acute respiratory distress syndrome, severe Dengue fever, malaria, and sepsis. The condition can lead to septic shock and multiorgan failure. However, at present there is no effective treatment to maintain vessel stability.

The team, led by Dr Pipsa Saharinen at the University of Helsinki, Finland, has looked at the possibility of inhibiting this permeability by targeting vascular integrins.

Integrins are receptors on the cell surface that oversee the interactions between cells and the extracellular matrix they are surrounded by. Beta1-integrin is present in endothelial cells on the surface of blood vessel walls.

The protein is already known to regulate the formation of blood vessels and keep them stable. The team searched for the potential role it could play in vascular leakage.

They found that a specific molecule that normally keeps vessels stable, does the opposite during inflammation, creating destabilisation and leakage. This process was seen to be mediated by beta1-integrin.

The findings were published in Proceedings of the National Academy of Sciences.

The team also found in studies on mice that a monoclonal antibody drug that targets beta1-integrin can hold back this vascular leakage.

Dr Saharinen said: "Sepsis may develop unexpectedly and proceed fast. When the patients arrive at the hospital, the disease may have already progressed. It would be important to have the means to inhibit vessel leakiness and the development of a more severe diseases.

"In our study, the antibody against beta1-integrin was effective in inhibiting vascular leak in mice even when it was administered after the onset of the leakage."


Source: Hakanpaa, L., Kiss, E.A., Jacquemet, G., Miinalainen, I., Lerche, M., Guzmán, C., Mervaala, E., Eklund, L., Ivaska, J. and Saharinen, P., 2018. Targeting β1-integrin inhibits vascular leakage in endotoxemia. Proceedings of the National Academy of Sciences, p.201722317.

Link: http://www.pnas.org/content/early/2018/06/22/1722317115

 

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