Study reveals hyperactive immune cells accelerate heart valve disease

Using organ-on-a-chip technology is revealing how overactive immune cells can aggravate heart valve disease and how it could potentially be controlled.

The study, led by RMIT University and the Baker Heart and Diabetes Institute, combined clinical work, such as blood samples and valve measurements, with lab experiments using organ-on-a-chip technology that replicated the pathological conditions inside the aortic valve.

Aortic valve stenosis is a degenerative condition that narrows the valve opening and reduces blood flow. Blood cells that need to squeeze through the narrow valve come under intense frictional force, known as shear stress. It is the most common type of heart valve disease in the elderly affecting more than one in eight people aged over 75 and if left untreated it has a higher mortality than most cancers.

Co-chief research investigator Dr Sara Baratchi said that in someone with severe aortic valve stenosis, circulating blood cells come under heavy shear stress about 1500 times a day. The ARC DECRA Fellow and Senior Lecturer at RMIT also said that this constant frictional force makes the white blood cells hyperactive.

“If we can stop that inflammatory response, we can hope to slow down the disease. The same organ-on-a-chip technology that helped us make these discoveries will also enable us to easily test potential drugs to treat this harmful immune response,” she said.

Co-chief investigator Dr Karlheinz Peter, Deputy Director of Basic and Translational Research at the Baker Heart and Diabetes Institute, said the study also helped explain why aortic valve stenosis can start to worsen dramatically, often over just a few months.

“The smaller the narrowing, the more the inflammatory cells get activated, and then they accelerate the disease,” Dr Peter said.

“Our study also shows that a valve replacement – either through open heart surgery or via a catheter-based percutaneous approach – not only improves blood flow but also acts as an anti-inflammatory measure. The latter is a novel and centrally important discovery.”

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