New Insights into Blood Flow Fluctuations to Aid Fight Against Cardiovascular Disease

Atherosclerosis, characterized by the narrowing of arteries due to fat and cholesterol buildup, is a leading cause of death in Western societies, contributing to approximately 50% of all deaths. This condition can lead to severe health problems including strokes, heart attacks, and dementia. The narrowing of arteries disrupts normal blood flow, which triggers a series of cellular responses including the activation of the body’s innate immune cells, the white blood cells. One specific response to these blood flow changes, known as shear stress, is NETosis. During this process, neutrophils, a type of white blood cell, release web-like structures to capture and neutralize pathogens. However, this mechanism also contributes to arterial blockage, promoting dangerous inflammation and blood clotting. Researchers have now discovered how these blood flow fluctuations exacerbate inflammation and clot formation, highlighting the pivotal role of blood flow-driven forces in cardiovascular disease progression.

Based on these new insights, researchers at the Baker Heart and Diabetes Institute (Melbourne, VC, Australia) have identified an intervention target that could reduce these harmful effects. The study has discovered that the Piezo1 ion channel on cells is a key player in NETosis. It responds to the mechanical stress from altered blood flows by allowing calcium into the cells, which then initiates NETosis, leading to inflammation and clotting. Published in Nature Communications, these findings suggest that blocking Piezo1 could be an effective therapeutic strategy to counteract the negative impacts of shear stress. Such a strategy holds considerable promise for improving treatments for atherosclerosis and other related conditions, potentially delivering substantial public health benefits.

“Blood flow-driven forces, like shear stress, play a critical role in the development and progression of various cardiovascular diseases, including atherosclerosis and heart valve disease,’ said Sara Baratchi, Associate Professor at Baker Institute Head of the Mechanobiology and Microfluidics lab. “Understanding the effect of shear stress in areas where blood vessels or heart valves are narrowed because of the immune cells is crucial in the context of cardiovascular disease, as it offers significant insights into the mechanisms that drive disease progression and complications. With these findings, we’re now a step closer to identifying protective treatments that can prevent this harmful clotting that is induced by the NETosis process.”

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Baker Heart and Diabetes Institute