GPR68 protein senses blood flow and tells arteriole blood vessels when to dilate. Researchers have identified this protein and think that medications which activate this protein may be useful to treat cardiovascular conditions such as ischemic stroke, as published in the journal Cell. To assess vascular health non-invasive clinical test flow mediated dilation is which informs doctors of vascular system health. Compromised flow mediated dilation is precursor to a range of vascular diseases including atherosclerosis and hypertension. It is an important process in which all of the molecules within the arteries to sense blood flow have been unknown. Arterioles which don’t dilate properly leave few options for lowering blood pressure in individuals with hypertension, or getting blood through clogged vessels in atherosclerosis.
The project to find GPR68 and investigate how it works the team designed a machine which uses of turbulent liquid movement to stand in for blood flow within vessels, using 384 pistons which move fluids around over a bed of cells placed in 384 wells on a plate, the motion simulates how blood would apply pressure to those cells, which tested a series of cell lines, some had mutations leading to overexpression of proteins linked to pressure sensing. Screening was performed on expression of candidate genes in all 384 wells, testing each gene to determine if it was required for responding to the machine turbulent pressure. Testing pointed to GPR68, further experiments suggested that it was essential for FMD and proper function of the vascular system.
GPR68 will be the focus of the teams future work, exploring clinically relevant cardiovascular diseases, and exploring possible use of other small molecules to modulate its function.