Molecule That Dilates Blood Vessels Hints at New Way to Treat Heart Disease


Source: The Scripps Research Institute

Summary: Researchers have identified a protein, called GPR68, that senses blood flow and tells small blood vessels called arterioles when to dilate.


Americans die of heart or cardiovascular disease at an alarming rate. In fact, heart attacks, strokes and related diseases will kill an estimated 610,000 Americans this year alone. Some medications help, but to better tackle this problem, researchers need to know exactly how the heart and blood vessels stay healthy in the first place. It has been known for decades that blood vessels sense changes in blood flow rate. Researchers from the Scripps Research Institute have identified a protein, called GPR68, that senses blood flow and tells small blood vessels called arterioles when to dilate. This information is crucial in regulating blood vessel dilation and controlling vascular tone. They believe medications that activate GPR68 could one day be useful to treat medical conditions, including ischemic stroke. The study findings were published in the journal Cell.

GPR68

To test how cells respond to sheer stress, the researchers designed a machine that uses turbulent movement of liquid to stand in for blood flow in blood vessels. Credit: Ardem Patapoutian and Jie Xu

The team started by designing a machine that uses the turbulent movement of liquid to stand in for blood flow in blood vessels. This machine uses 384 pistons that move the fluid up and down over a bed of cells, placed in 384 wells on a plate. This motion simulates how blood would put pressure on those cells. They performed a screen, knocking down the expression of different candidate genes in each of the 384 wells, and tested if that gene is required for responding to the machine’s turbulent pressure. The tests pointed the researchers to GPR68, which the authors showed works as a sensor of mechanical stimulation. Further experiments suggested that GPR68 is essential for flow-mediated dilation.

Prof. Ardem Patapoutian said, “Future work will explore the role of GPR68 in clinically relevant cardiovascular diseases”, “We are also exploring the possibility of using small molecules to modulate the function of GPR68, as such molecules could be beneficial in the clinic.”


More Information: Jie Xu et al, “GPR68 Senses Flow and Is Essential for Vascular Physiology”, Cell (2018). DOI: https://doi.org/10.1016/j.cell.2018.03.076


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