Scientists Identify Previously Undiscovered Role of Enzyme in Regulating Blood Pressure

Breakthrough could lead to new therapies for hypertension

In a study published online in Nature Biotechnology, scientists at the Feinstein Institute for Medical Research in New York and at the Karolinska Institute in Sweden have discovered that T-cells capable of producing the neurotransmitter acetylcholine can regulate blood pressure. These T-cells are white blood cells, part of the immune system, which contain the enzyme choline acetyltransferase (ChAT). ChAT enzymes are responsible for the production of acetylcholine.

“Previous studies conducted at the Feinstein Institute found that the immune function could be controlled by neural mechanisms through the spleen, and with this study we were looking to identify triggers that could reach deeper into the smaller arteries to aid with conditions such as high blood pressure,” said co-lead author Kevin J. Tracey, MD “We found what we were looking for, and will develop this finding into new research that we hope will pave the way to new therapies that will improve the lives of millions.”

In 2011, a Feinstein Institute paper published in Science described how T-cells in the spleen express ChAT, which can affect immune function under the control of the vagus nerve. The new research published in Nature Biotechnology aimed to further examine T-cells that synthesize via ChAT vasorelaxant acetylcholine, which affects blood pressure. When observing mice in this study, the researchers found that those without ChAT in their T-cells developed hypertension. This led to the conclusion that the source of acetylcholine that affects arterial pressure is these T-cells.

Having identified the new role for ChAT cells and knowing that these cells respond to vagus-nerve stimulation, the Feinstein Institute researchers plan to explore the use of bioelectronic medicine to treat blood pressure and hypertension––a condition that affects more than 70 million Americans.

All major organs of the body are innervated, allowing the brain to both monitor and regulate organ function. Bioelectronic medicine leverages these neural pathways to regulate therapeutic targets and treat disease, according to the Feinstein Institute. Nerve-stimulating or nerve-blocking devices, either implanted on a nerve or held against the skin, have the potential to modulate specific nerve activity, to elicit a specific change in organ function, and to restore health without the complicated adverse effects of pharmaceutical agents, the Institute says. Such devices are already in clinical trials to treat inflammatory diseases, such as rheumatoid arthritis (RA) and colitis.

RA, a disease of the immune system, is characterized by harmful inflammation in the joints. Pharmaceutical agents developed for the disease, including monoclonal antibodies, have harmful and sometimes lethal adverse effects. Investigators at the Feinstein Institute discovered in the late 1990s that electrical stimulation of the vagus nerve could turn off the immune-system pathways associated with RA, colitis, and other inflammatory diseases. This technology has been licensed to a biotechnology company, SetPoint Medical, and clinical trials of its new bioelectronic medicine device are under way in subjects with RA or colitis.

Sources: Northwell Health; September 12, 2016; Nature Biotechnology; September 12, 2016; and Feinstein Institute; 2016.