Controlling the microbiome improves heart disease

A Cleveland Clinic study published in the journal Nature Communications found that phenylacetylglutamine (PAG), produced by gut bacteria as a waste product, then taken up and synthesized in the liver, interacts with previously unknown sites on the beta-2 adrenergic receptor of heart cells entering the bloodstream.

PAG interacts with beta-2 adrenergic receptors to influence how heart muscle cells contract, a process researchers believe contributes to heart failure. The researchers showed that changing parts of the beta-2 adrenergic receptor previously thought to be unrelated to signaling activity in previous models prevented the PAG from depressing receptor activity.

They also demonstrated that the PAG signaling pathway of the gut microbiota has been mechanistically linked to several characteristics related to heart failure and cardiovascular disease risks.

Beta blockers, commonly used to treat heart failure and blood pressure, act on the body’s “fight or flight” response. This critical response is controlled by beta adrenergic receptors and is essential for survival, but repeating this response over time can lead to chronic damage to the heart, contributing to the development of heart failure.

Beta blockers are designed to fit into the same keyhole, preventing adrenaline and other hormones from binding to beta-2 adrenergic receptors. This, in turn, slows the heart rate, reduces stress on the heart, and opens blood vessels. Previous studies by this research group found that circulating levels of the PAG are associated with heart failure detection and severity indicators, and that the PAG directly promotes features related to heart failure, including heart failure. weak The adverse effects of PAG on relevant aspects of heart failure are modified by the use of a common beta-blocker in preclinical models, strengthening the link between PAG, heart failure, and beta-adrenergic receptors.

His team’s findings point to a completely new way to develop drugs that regulate the beta-2 adrenergic receptor, a more nuanced process than what is currently on the market. They are currently working to develop drugs that target the PAG pathway and its interactions with adrenergic receptors as a new drug approach to treat cardiovascular diseases.