Shear Stress in the Aging Heart Makes Immune Cells Inflammatory, Accelerating Cardiovascular Disease

Researchers here note a process by which the hardening of heart valves, known as aortic valve stenosis, accelerates in its later stages. The condition causes greater shear stress in blood flow, which in turn causes immune cells in the bloodstream to become more inflammatory. The resulting greater chronic inflammation in heart tissue accelerates the mechanisms that cause stenosis. This hardening of tissue is due to calcification; a growing fraction of cells in the valves adopt behaviors more appropriate to bone tissue, creating calcium structures. Inflammatory signaling, such as that produced by the presence of senescent cells in aged tissues, is known to contribute to this inappropriate cellular activity.

Aortic valve stenosis is the most common type of heart valve disease in the elderly and affects more than one in eight people aged over 75. The condition is typically caused by degeneration and thickening of the aortic valve, which narrows the valve opening and reduces blood flow. Blood cells that have to squeeze through the narrow valve come under intense frictional force, known as shear stress. A team of researchers and clinicians set out to investigate the effect of this shear stress on white blood cells - key players in our immune system's first line of defense. They found the constant stress of squeezing through the narrow aortic valve activates these cells, leading to harmful inflammation that accelerates the progression of aortic stenosis.

The team have identified a potential drug target by pinpointing the receptor that controls this white blood cell overactivity. The research 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. "In someone with severe aortic valve stenosis, circulating blood cells come under heavy shear stress about 1500 times a day. We now know 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."


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