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Saying NO to blood vessel complications

Project summary

Nitric oxide (NO) is a naturally occurring chemical inside the body that protects our blood vessels. In type 2 diabetes, levels of NO are lower than normal. Dr Katie Simmons wants to work out why and how we can restore it, to keep blood vessels in people with type 2 diabetes healthy. With more research, this could lead to the development of a new treatment to prevent blood vessel complications like heart attacks and strokes.

Background to research

Nitric oxide (NO) is a protective chemical which is important in maintaining healthy blood vessels. There are two other chemicals that work together to control the levels of NO in the body. These are called endothelial nitric oxide synthase (eNOS) and proline rich tyrosine kinase-2 (PYK2).

In people with type 2 diabetes, the levels of PYK2 are higher than normal, upsetting the balance with eNOS. As a result, there are lower levels of protective NO inside the blood vessels. Having healthy, fully functioning blood vessels is key to preventing complications like heart attacks and strokes.

Dr Simmons wants to study how eNOS and PYK2 work together to increase the levels of protective NO inside blood vessels, to find out how to improve blood vessel health.

Research aims

Dr Simmons will study eNOS and PYK2 in the lab, looking at how they interact with each other using a sophisticated technique called ‘Surface Plasmon Resonance’. This involves attaching one of the chemicals (eNOS or PYK2) to a gold chip which sits inside a machine. When the second chemical is added, the machine measures changes on the surface of the gold chip. This information helps Dr Simmons to understand how the two chemicals interact with each other.

She will use a second technique to study interactions between the two chemicals, called ‘Isothermal Titration Calorimetry’. This uses very sensitive thermometers to detect the difference in temperature between two containers: one holds eNOS or PYK2 on its own, and the other holds both chemicals together. By analysing the difference in temperature between the two containers, Dr Simmons can calculate how much the two chemicals interact.

Potential benefit to people with diabetes

A greater understanding of how to keep blood vessels healthy will help pave the way for more research to develop new treatments for people with type 2 diabetes that work to prevent complications like heart attacks and strokes.

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