New Insights on the Formation and Malformation of Blood Vessels

Diabetes, cancer, rheumatism and stroke are some of the diseases that are capable of developing a disorder in the blood vessels. This could exacerbate the condition and obstruct treatment. A research team from Karolinska Institutet has shown how the //blood vessels could normally change their size to create a functional circulatory system and how the vascular malformation during a disease could occur.

In the study, published in Nature Cell Biology, the researchers managed to treat vascular malformation in mice, a discovery of potential significance to numerous vascular diseases.

A healthy body has a perfect balance of arteries, capillaries and veins that allow the blood to reach every cell in the body and that form what is called the "vascular tree". New blood vessels are formed by endothelial cells, which normally coat the inside of blood vessels and which organize themselves into tubes and mature, along with other cells, into arteries, capillaries or veins.

Throughout a person's life, the vascular tree has to adapt its branches to the changing needs of body tissue, such as during growth, muscle building or wound healing. However, there are diseases that affect the endothelial cells in a way that throws the vascular tree out of balance, which exacerbates the disease and often causes hemorrhaging.

In cancer, for example, it is known that the vessels leak and direct shunts form between arteries and veins, preventing drugs from reaching the tumor.

To understand how arteries, veins and capillaries are created - and how the process malfunctions in the presence of disease - the researchers studied normal vascular formation and the inherited Osler-Weber-Rendu disease (HHT), which is characterized by vascular malformation and repeated hemorrhaging, with an increased risk of stroke.

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By switching signals on and off in the endothelial cells of genetically manipulated mice, the researchers could describe how the protein Endoglin controls vascular formation and malformation. They found that the protein acts like a sensor that detects blood flow and tells the endothelial cells to organize themselves into veins, capillaries or arteries as necessary. Cells that lacked the protein were less able to form arteries.

The researchers were also able to reduce vascular malformation in the genetically manipulated mice.

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"Our findings contribute to the understanding of fundamental biological processes that explain how the vascular tree is formed and what causes vascular malformation," says Lars Jakobsson, assistant professor at Karolinska Institutet's Department of Medical Biochemistry and Biophysics. "Drugs with a similar effect as one of those we tested are currently used to treat patients with inherited vascular malformation but are still under evaluation.

Now we have another candidate and a more nuanced idea of how it works. We are now in a better position to control the formation and malformation of blood vessels and thus their function, which can eventually lead to improved treatments for a number of diseases."

The researchers at Karolinska Institutet also contributed to a parallel study, published in the same issue of Nature Cell Biology, describing how blood flow influences endothelial cell size that in turn affects vessel identity and malformation.



Source-Eurekalert