Researchers ID protein that can be activated to treat heart disease

April 20 (UPI) — Scientists at a private research institute have identified a protein in blood vessels that potentially can be activated by drugs to treat heart disease.

The protein, called GPR68, senses blood flow and can dilate small blood vessels called arterioles, according to researchers at The Scripps Research Institute in La Jolla, Calif. The findings were published this week in the journal Cell.

“It has been known for decades that blood vessels sense changes in blood flow rate, and this information is crucial in regulating blood vessel dilation and controlling vascular tone,” senior author Dr. Ardem Patapoutian, a Scripps Research professor and Howard Hughes Medical Institute investigator said in a Scripps press release.

Heart attacks, strokes and related diseases will kill an estimated 610,000 Americans this year alone, according to the Centers for Disease Control and Prevention. It is the leading cause of death for men and women.

The researchers believe that once they exactly know how the heart and blood vessels stay healthy, it can lead to medical treatments better than any currently available.

Flow-mediated dilation, a non-invasive clinical test, indicates the health of the vascular system. When FMD is compromised, it’s an indication of a variety of vascular diseases, including hypertension and atherosclerosis.

Because arterioles can’t dilate properly, the body can’t as easily lower blood pressure in people with hypertension or move blood through clogged vessels in atherosclerosis.

“Despite the importance of this process, the molecules involved within arteries to sense blood flow have remained unknown,” Patapoutian said.

Patapoutian led the project to find GPR68 and determine how it works with Dr. Jie Xu, a postdoctoral fellow in the lab and now an independent scientist at the Genomics Institute of the Novartis Research Foundation.

They designed a machine that simulates blood floor with turbulent movement of liquid. In this system, 384 pistons move the fluid up and down over a bed of cells placed in 384 wells on a plate.

They tested cell lines, including some mutated ones that led to additional proteins.

Then they cut down the different candidate genes in each of the 384 wells, seeing if that gene is required for responding to the machine’s turbulent pressure.

They narrowed it to GPR68, which they found is essential for FMD.

“In a model organism, this protein is essential for sensing blood flow, and the proper functioning of the vascular system,” Patapoutian said.

In future research, they plan to explore “the possibility of using small molecules to modulate the function of GPR68, as such molecules could be beneficial in the clinic.”

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