Novel and Emerging Technologies (NET) Grant (PhD studentship)
Prof David Firmin and Dr Andrew Scott, Royal Brompton Hospital and Imperial College London
Summary: Inflammation is a protective mechanism activated by the body’s immune system to fight infection, remove harmful toxins and help in the healing process. However, inflammation can also harm the human body, especially when it does not resolve and becomes persistent. It is now known that chronic inflammation plays an important role in the development of cardiovascular disease, particularly atherosclerosis – the build-up of fatty material inside blood vessels. In the presence of risk factors for cardiovascular disease, such as obesity, high cholesterol and high blood sugar, the lining of blood vessels becomes damaged, and this leads to the production of inflammatory chemicals. Some of these chemicals are harmful to the blood vessels and promote atherosclerosis, while others are protective. Understanding the mechanisms that lead to persistent inflammation and cause damage to blood vessels is therefore very important so that steps can be taken to counteract them.
Prof Khan’s team has recently identified a group of enzymes, called salt-inducible kinases or SIKs, which inhibit the production of protective anti-inflammatory chemicals. Importantly, they have shown that when the SIKs are switched off using drugs, there is an increase in the production of protective anti-inflammatory chemicals and a reduction of harmful pro-inflammatory chemicals. Using laboratory models of atherosclerosis, this project will investigate the role of SIKs in the development of atherosclerosis. Importantly, they will test whether switching off the SIKs helps to reduce the development of atherosclerosis.
The findings will help to determine whether inhibiting SIKs can protect against processes responsible for the early development of atherosclerosis. By inhibiting the harmful pro-inflammatory pathways and promoting the protective anti-inflammatory pathways, drugs that inhibit the SIKs could lead to new treatments for cardiovascular disease. It is hoped that the findings may pave the way for clinical trials of SIK inhibitors in patients with cardiovascular disease.
In future studies, the research team hopes to extend the findings from the laboratory models to patients admitted to hospital with an acute heart attack. Previous studies show that such patients have high levels of inflammation in the body that contribute to the complications linked with acute heart attacks, and the team plans to examine whether high levels of SIKs play an important role in cardiovascular disease in these patients.