Targeting heart disease by focusing on a protein that dilates blood vessels

Cardiologists often use a test called flow-mediated dilation (FMD) to detect abnormalities in blood flow that can be an early warning sign of diseases such as hypertension and atherosclerosis. But identifying the molecules in the body that are responsible for impeding or facilitating blood flow has been challenging.

Now scientists at the Scripps Research Institute in La Jolla, California, have pinpointed a protein that can sense blood flow and prompt tiny blood vessels called arterioles to dilate. They believe the protein, called GPR68, could be a valuable target for drug development. They described the discovery in the journal Cell.

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The team, helmed by Scripps professor Ardem Patapoutian, Ph.D., started by building a machine that mimics blood flow. The machine moves fluid over cells in plates, simulating the way blood exerts pressure on cells in the body, according to a press release. 

The cell lines the researchers used had genetic mutations linked the overexpression of proteins that are suspected to influence pressure sensing. By systematically knocking down different genes, and then observing how cells responded to the turbulence created by the machine, they landed on GPR68. 

Maintaining the healthy functioning of arterioles is important, because when they can’t dilate, blood pressure can rise or blood vessels can become clogged. “In a model organism, [GPR68] is essential for sensing blood flow, and the proper functioning of the vascular system," Patapoutian said in the statement.

Cardiovascular disease is the leading cause of mortality in the U.S., accounting for about 1 in every 4 deaths, according to the Centers for Disease control. The search for cures has inspired the creation of everything from a fully functional, beating heart patch that Duke engineers made from stem cells, to a tiny, injectable heart patch created at the University of Toronto.

In January, a team of Spanish researchers published evidence that a giant protein called titin plays a key role in regulating the ability of cardiac muscle cells to contract properly.

The next step for the Scripps team is to further study how GPR68 influences various 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," Patapoutian said.