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The complexities of the blood vessel system and angiogenesis

If all of your blood vessels were aligned in a straight line, the length of the new line would be greater than the distance of travelling around the world twice. A lots of blood vessels for just one body; and it all needs looking after.

As a human, you weren’t born your current size, meaning your blood vessels also needed to grow. The name of this process is called angiogenesis.

Scientists and drug companies are very interested in this process, for a very surprising and potentially lucrative reason.

Worldwide, abnormal angiogenesis is thought to contribute to disease in around one billion people. It’s no wonder then, that over $4 billion has been invested into drug research and development, making this one of the highest funded areas of medical research in history. But… there’s a problem; the current angiogenic therapies are not very effective.

You might be thinking some of these questions at this point: how does angiogenesis contribute to so much disease? And why have we not got any effective therapies? One needs to understand normal angiogenesis before they can understand the answers to these questions.

Normal angiogenesis can be split in to two parts; the first of which is blood vessel maintenance. All of your blood vessels are lined by endothelial cells, which are in close contact with another group of cells called pericytes. Together they create a small space called a basement membrane, into which the pericytes secrete small numbers of special chemicals. These chemicals induce angiogenesis, and are called pro-angiogenic factors. The endothelial cells need a small amount to live on, which is why the number of these is so small.

If this amount is raised, then the second part of angiogenesis might occur. This is where blood vessels grow from preexisting vessels. This depends on a balance between pro-angiogenic factors and another group of chemicals that try to stop it, known as anti-angiogenic factors. It is the balance of these factors that decides when the second part of angiogenesis occurs.

When the balance favours pro-angiogenic factors, the endothelial cells start acting different. One cell – called the “tip” cell – becomes extra-active, and grows out of the blood vessel to find somewhere to go to. This ‘somewhere’ is usually another blood vessel or another tip cell. They join and a new blood vessel is formed.

But, you ask, how can two tip cells make a new blood vessel, and how does the tip cell “know” where to go? They don’t, and they don’t “know.”.

When a tip cell grows it senses chemicals in the surrounding tissue that changes the cell’s behaviour so that it goes somewhere appropriate. When it travels, the cells beside the tip cell divide and divide, so that the neighbour cell clones follow the tip cell until it finds somewhere to stop. Finally, blood flows through this new vessel and the first part of angiogenesis occurs.

So, how is angiogenesis involved in so many diseases? This is dependant on the disease, but it might not be so surprising when you think about it. Either too much angiogenesis occurs or too little. In too little the tissue dies of oxygen starvation, and this occurs in things like coronary artery disease.

When there are too many blood vessels this can cause a number of things to happen, including the release of too much fluid, or even oxygen starvation from misdirecting blood flow away from starving tissues. The latter example occurs in diseases like cancer and some eye diseases.

So with this knowledge, why has there been no success with designing drugs, especially when so much money has been invested? There isn’t a clear answer to this, other than we simply don’t know enough about angiogenesis.

For example, there are anti-angiogenic drugs used to starve cancerous tissue (which grows its own blood vessels). The cancerous cells, however, are thought to grow more cancerous when deprived of oxygen, which is thought to increase the severity of problems.

Thus, scientists are thinking that increasing blood flow might be a better idea as it limits the bad cancer cells which spread around the body from forming. Though paradoxically, the local cancer will grow more quickly.

A lot to think about for the future study of angiogenesis. An area of research which will continue to grow.

Oliver Davis

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