Study identifies new treatment target for sleep apnea

Specialized channel proteins are possible therapeutic targets for sleep apnea and similar abnormally slow breathing disorders in obese people, suggest Johns Hopkins Medicine researchers who did a study on mice.

November 5, 2022

Health

5 min

zeenews

Washington [US], November 5 (ANI): According to Johns Hopkins Medicine researchers who conducted a study on mice, specialized channel proteins are potential therapeutic targets for sleep apnea and other unusually slow breathing issues in obese humans.
The carotid bodies, which are tiny sensory organs in the neck that sense changes in oxygen and carbon dioxide, as well as some blood-borne hormones like leptin, include the protein TRPM7, a cation channel. The flow of positively charged molecules into and out of the cells of the carotid bodies is regulated and transported by TRPM7 proteins.
The current study, conducted at the Polotsky Research Lab at Johns Hopkins Medicine and directed by postdoctoral fellow Lenise Kim, PhD, expands on earlier findings from the lab that indicated TRPM7 was involved in the progression of high blood pressure in mice.
The most recent research, which was detailed in a publication that was first published on October 10 in The Journal of Physiology, showed that TRPM7 is involved in restricting breathing in obese mice who exhibit symptoms of sleep-disordered breathing.
Up to 45% of obese Americans are thought to experience sleep-disordered breathing, which is defined by breathing that comes and goes throughout sleep.
If left untreated, the illness can exacerbate diabetes and heart disease, lead to severe exhaustion, and even result in death from inadequate oxygenation. Although CPAP therapy is frequently poorly accepted by patients, lifestyle modifications like weight loss and regular usage of CPAP machines can help treat sleep apnea.
“CPAP actually works for most patients, the fact is that most patients are not adherent to this treatment,” says Kim. “So knowing that TRPM7 contributed to high blood pressure and sleep-disordered breathing, we wondered if blocking or eliminating that channel could offer a new treatment target.”
Using silencing RNA, the researchers knocked out the gene responsible for producing the TRPM7 channel protein, reducing the number of TRPM7 channels in the carotid bodies of obese mice. Mice then underwent a sleep study, during which researchers observed their breathing patterns and blood oxygen levels.
The amount of air inhaled and expelled by the lungs per minute was significantly different in obese mice with blocked TRPM7 than in normal mice. The minute ventilation of the obese mice increased by 14% as they slept, reaching 0.83 milliliters of air per minute per kilogram (mL/min/g).
When compared to obese mice with TRPM7, whose average minute ventilation was 0.73 mL/min/g, researchers claim that these data show a considerable improvement in ventilation. These results demonstrate that these mice’s ventilatory capacity was enhanced as they slept, successfully reversing the reduced breathing patterns associated with sleep apnea.
Notably, the researchers discovered that even while fat mice without TRPM7 had greater breathing, their blood oxygen levels remained the same. The mice were placed in hypoxic, or low-oxygen, conditions, and the researchers then observed the mice’s breathing patterns to come to this conclusion.
The mice’s bloodstream oxygen levels declined even though their minute ventilation increased by 20%, from 1.5 mL/min/g to 1.8 mL/min/g, indicating that their greater inhalations did not assist saturate the body with more oxygen.
“This suggests that treatments designed to reduce or erase TRPM7 in carotid bodies would not be workable for people living in low-oxygen environments, such as those in very high altitudes, or for those with conditions that already limit blood oxygen saturation, such as lung disease,” says Kim.
The research team’s findings also show that leptin, a hormone that is produced in fat cells and regulates hunger, may result in an increase in TRPM7 channels. TRPM7 levels and production are already known to be accelerated by leptin in carotid bodies.
Leptin levels may rise in obese mice because they have more fat cells, which could cause TRPM7 to become overstimulated. The decreased respiration rates seen in obese mice with TRPM7 may, in turn, be a result of these high cation channel concentrations.
“We have shown that the genetic knockdown of TRPM7 in carotid bodies reduces suppressed respiration in sleep-disordered breathing,” says Vsevolod (Seva) Polotsky, M.D., Ph.D., director of sleep research and professor of medicine at the Johns Hopkins University School of Medicine. “While more research is needed, carotid body TRPM7 is a promising therapeutic target not only for hypertension in obesity but also for abnormal breathing during sleep associated with obesity.” (ANI)

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