Hints At New Way To Treat Heart Disease2 years, 1 month ago
Posted on Apr 24, 2018, 11 p.m.
Cardiovascular disease will kill an estimated 610,000 Americans this year alone, people die at an alarming rate due to heart attacks, strokes, and related diseases. There are some medications which help, but more research is needed to tackle this problem more efficiently.
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.
Materials provided by Scripps Research Institute.
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Jie Xu, Jayanti Mathur, Emilie Vessières, Scott Hammack, Keiko Nonomura, Julie Favre, Linda Grimaud, Matt Petrus, Allain Francisco, Jingyuan Li, Van Lee, Fu-li Xiang, James K. Mainquist, Stuart M. Cahalan, Anthony P. Orth, John R. Walker, Shang Ma, Viktor Lukacs, Laura Bordone, Michael Bandell, Bryan Laffitte, Yan Xu, Shu Chien, Daniel Henrion, Ardem Patapoutian. GPR68 Senses Flow and Is Essential for Vascular Physiology. Cell, 2018; 173 (3): 762 DOI: 10.1016/j.cell.2018.03.076