Pulmonary hypertension is a critical condition that often results in heart failure and death for many patients. In search of innovative treatment methods, a team led by Professor Daniela Wenzel and Dr. Alexander Seidinger from the Department of Systems Physiology at Ruhr University Bochum, Germany, explored the potential of a plant-derived compound, FR900359 (FR), to combat this disease (1^✔ ✔Trusted Source
Anti-hypertensive mechanisms of cyclic depsipeptide inhibitor ligands for Gq/11 class G proteins

Go to source

).

Exploring New Treatment Options for Pulmonary Hypertension

FR differs from existing treatments by targeting a unique point in the signaling pathway responsible for pulmonary hypertension. This allows it to inhibit multiple factors that cause vasoconstriction in the lungs simultaneously.

“In our experiments, FR relaxed the vessels quickly and effectively and produced a good therapeutic effect,” explained Seidinger, the study’s first author. The team’s findings were published in the journal EMBO Molecular Medicine on July 8, 2024.

Pulmonary hypertension occurs when blood vessels in the lungs contract and the surrounding smooth muscle layer thickens, causing blood pressure in the lungs to rise. This condition places immense stress on the right heart, which must exert greater force to pump blood through the lungs. Over time, the heart enlarges and can eventually fail.

“The causes of pulmonary hypertension are often obscure,” Seidinger notes. In his doctoral research, Seidinger aimed to discover new treatment options for this serious condition. Existing medications typically block individual receptors or signaling pathways that trigger vasoconstriction.

“However, there are many of these so-called vasoconstrictors,” Seidinger says. “And each one has its own receptor. A single blockade is therefore not very effective.”

Targeting Gq Proteins

The researchers adopted a different strategy by targeting a later stage in the signal transmission process. “Within the cells, there are only a few pathways through which the signal for vasoconstriction is passed on,” Seidinger explains. “Gq proteins are involved in many of these pathways, making them an ideal target for intervention.”

Previous studies had indicated that FR, derived from the plant Ardisia crenata, impacts Gq proteins. The researchers aimed to use FR to inhibit various vasoconstrictors equally. Initial tests on isolated pulmonary vessels from mice demonstrated FR’s effectiveness.

“FR quickly resulted in significant vascular relaxation,” Seidinger highlights. Subsequent tests on tissue from pigs and human samples confirmed this effect. Experiments on mice with pulmonary hypertension showed that FR treatment alleviated symptoms and significantly improved the animals’ health.

“The thickness of the muscle layer around the pulmonary vessels decreased—or didn’t even increase in the first place,” Seidinger explains.

The researchers observed only minor side effects, such as a slight drop in overall blood pressure, which could potentially be beneficial in treating pulmonary hypertension.

“FR could therefore be a promising drug candidate for the treatment of the disease,” Seidinger concludes. “However, it will certainly take many years of intensive research before it can be used in clinical practice.”

Reference:

1. Anti-hypertensive mechanisms of cyclic depsipeptide inhibitor ligands for Gq/11 class G proteins – (https://www.sciencedirect.com/science/article/abs/pii/S1043661818316025?via%3Dihub)

Source-Medindia