Building a blood vessel brick by brick

The principles of engineering tell us that if we can break a problem down to its fundamental components then we will be able to understand, improve and rebuild.

Imperial College Researchers Neil Dufton, Viktoria Kalna, Claudio Raimondi and Anna Randi apply the same principle to our blood vessels. As Neil tells us, the problem is that not all blood vessels are built the same way!

As winter sets in and we dig out our woolly socks and gloves we are all reminded just how crucial our circulation is to our happiness and wellbeing. Our blood vessels are ultimately responsible for regulating our temperature; dilating when we are too hot and constricting when the temperatures drop. The control of our body temperature shows how responsive our blood vessels are to changes in our environment but this is just the tip of the proverbial iceberg in terms of the huge number of jobs our blood vessels cope with on a daily basis.

Their responsibilities include distributing oxygen and nutrients, regulating blood pressure and acting as the body’s motorways for our immune cells. To carry out all these tasks, blood vessels range in size from our largest veins and arteries, 3–5cm in diameter, to tiny capillaries, such as in the whites of our eyes, that are a thousandth of a millimetre in size.

They combine to create a vast network that if laid end-to-end it would stretch more than three times around the world!

Three vessels: Image depicts the three types of blood vessel (from left to right) an artery, vein and capillary. Endothelial cells are light blue and smooth muscle cells are red. Arteries are made up of many endothelial cells wrapped in a very thick smooth muscle layer, this is in stark contrast to the tiny capillary which is formed by individual endothelial cells. (Neil Dufton, Imperial College)

The building blocks that make blood vessels are the same…but different?

All blood vessels, big and small, develop from one single cell type called endothelial cells (the blue cells in the above image). These specialised cells form the inner lining of the tube-like structures that we recognise as blood vessels.

However, despite being the same cell type the endothelial cells within an artery differ in their behaviour to that of a vein and again to the tiniest vessels called capillaries. This is particularly obvious in how they form surrounding structures, such as a thick layer of smooth muscle cells that surround arteries to ensure that the blood pressure from the heart is maintained (above).

Another brick in the wall: Endothelial cells link together to form a semi-permeable barrier within blood vessels. (Aarti Shah, Imperial College).

What makes our blood vessels go to pieces?

Endothelial cells interlock with each other to form a barrier between our blood and surrounding tissues. To do this they form junctions that zip tightly together creating a single layer of cells (left).

If we have an injury, like a cut finger, this barrier breaks down and our vessels become leaky (below) which we see and feel as heat, redness and swelling. The ‘destabilisation’ of blood vessels is crucial for tissue repair allowing new blood vessels to grow into the wound.

In chronic inflammatory diseases, like heart disease, leaky blood vessels are a serious problem because they function less efficiently and surrounding tissues become full of fluid making the heart work harder to compensate. It is also thought to be the first stage in developing a blockage within the blood vessel.

Leaky Vessel: Inflammatory diseases can cause blood vessels to become very unstable or leaky. Here we have imaged a leaky blood vessel (red) releasing fluorescent dye (grey) into the surrounding tissue using 3D microscopy. (Neil Dufton, Imperial College)

Can we build a better blood vessel?

In Professor Anna Randi’s research group at the National Heart and Lung Institute (Imperial College London) we are working to re-establish the integrity of our blood vessels to help prevent tissue damage.

One of the ways to do this is to profile the genes that regulate a ‘protective’ endothelial cell compared to a ‘leaky’ endothelial cell and determine if we can correct the problems that occur during disease.

By mimicking the genetic signature of a protective endothelial cell we can improve the barrier function and increase their association of regulatory cells (called mural cells), which help maintain blood vessel function.

Present and future therapies

There are currently no specific therapies that can re-stabilise blood vessels so, in the event that blood vessel damage leads to a blockage, doctors have to widen blood vessels surgically. This procedure is done by physically inserting a metal structure called a stent within the affected area.

The use of stents is very successful for normalising blood flow but does a huge amount of damage to the endothelial cells and surrounding tissue. Scientists hope that by developing drugs that target the endothelial cells we can restore the stability of blood vessels, repair the damaged tissue and prevent the need for surgery.

My colleagues and I will be building vessels brick by brick with Lego and talking about our work on Thursday the 24th November, as part of the Science In Store event taking place at the BHF Ealing Furniture and Electrical Store.

For more information on the event, visit the Science in Store page.