Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association

Active Plant Substance Reduces Pulmonary Hypertension

image: 

Daniela Wenzel, Michaela Matthey and Alexander Seidinger (from left) tested the effect of the substance FR on pulmonary hypertension.

 

view more 

Credit: © RUB, Marquard

What causes pulmonary hypertension

The blood pressure inside the lungs is typically much lower than in the rest of the body. Pulmonary hypertension occurs when the blood vessels within the lungs contract and the smooth muscle layer surrounding these vessels thickens. The disease puts constant stress on the right heart, as it needs considerably more strength to pump the blood through the lungs. As a result, the heart becomes enlarged and may eventually fail due to overload. "The causes of pulmonary hypertension are often obscure," points out Alexander Seidinger.

As part of his doctoral thesis, he focused on finding new treatment options for this serious disease. Current drugs are based on blocking individual receptors or signaling pathways that transmit the signal to constrict the pulmonary vessels. "However, there are many of these so-called vasoconstrictors," says Alexander Seidinger. "And each one has its own receptor. A single blockade is therefore not very effective."

Gq proteins make a promising target

The researchers chose a different approach: Rather than targeting the signal transmitter, it intervenes at a later stage in signal transmission. "Within the cells, there are only a few pathways through which the signal for vasoconstriction is passed on," explains Seidinger. "So-called Gq proteins are involved in many of these pathways. This makes them a good target for intervention."

Previous studies had shown that the substance FR from the plant Ardisia crenata, which is a common houseplant, has an effect on Gq proteins. The researchers therefore hoped to use FR to inhibit many different vasoconstrictors equally. They first tested the substance on isolated pulmonary vessels from mice and demonstrated its effectiveness. "FR quickly resulted in significant vascular relaxation," points out Alexander Seidinger. Subsequent tests on tissue from pigs and human samples confirmed this effect. In experiments on mice suffering from pulmonary hypertension, the researchers eventually showed that treatment with FR alleviated the symptoms and greatly improved the animals' state of health. "The thickness of the muscle layer around the pulmonary vessels decreased – or didn't even increase in the first place," says Seidinger.

The researchers only observed minor side effects: The blood pressure dropped slightly throughout the body. In fact, this could be beneficial in the treatment of pulmonary hypertension. "FR could therefore be a promising drug candidate for the treatment of the disease," concludes Alexander Seidinger. "However, it will certainly take many years of intensive research before it can be used in clinical practice."

Cooperation partners

In addition to the researchers from Systems Physiology at Ruhr University Bochum, researchers from the Pharmacology Research Group, University Hospital of Nottingham, UK, Massachusetts General Hospital and Harvard Medical School, Boston, USA, the University of Bonn and the University Hospital of Ruhr University Bochum in Bad Oeynhausen collaborated on the study.

Journal

EMBO Molecular Medicine

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Pharmacological Gq Inhibition Induces Strong Pulmonary Vasorelaxation and Reverses Pulmonary Hypertension

Article Publication Date

8-Jul-2024

Disclaimer: AAAS and EurekAlert! Are not responsible for the accuracy of news releases posted to EurekAlert! By contributing institutions or for the use of any information through the EurekAlert system.

Active Plant Substance Found To Reduce Pulmonary Hypertension

Pulmonary hypertension is a very serious disease that leads to heart failure and death in many patients. Searching for new treatment options, a team headed by Professor Daniela Wenzel and Dr. Alexander Seidinger from the Department of Systems Physiology at Ruhr University Bochum, Germany, tested the plant substance FR900359—referred to as FR by the researchers.

It differs from previously used active substances in that it targets a different point in the signaling pathway that leads to pulmonary hypertension. As a result, it simultaneously inhibits numerous factors that lead to vasoconstriction in the lungs.

"In our experiments, FR relaxed the vessels quickly and effectively and produced a good therapeutic effect," as Seidinger, first author of the study, outlines the findings. The results were published in the journal EMBO Molecular Medicine on July 8, 2024.

The blood pressure inside the lungs is typically much lower than in the rest of the body. Pulmonary hypertension occurs when the blood vessels within the lungs contract and the smooth muscle layer surrounding these vessels thickens. The disease puts constant stress on the right heart, as it needs considerably more strength to pump the blood through the lungs.

As a result, the heart becomes enlarged and may eventually fail due to overload. "The causes of pulmonary hypertension are often obscure," points out Seidinger.

As part of his doctoral thesis, he focused on finding new treatment options for this serious disease. Current drugs are based on blocking individual receptors or signaling pathways that transmit the signal to constrict the pulmonary vessels.

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

Gq proteins make a promising target

The researchers chose a different approach: Rather than targeting the signal transmitter, it intervenes at a later stage in signal transmission. "Within the cells, there are only a few pathways through which the signal for vasoconstriction is passed on," explains Seidinger. "So-called Gq proteins are involved in many of these pathways. This makes them a good target for intervention."

Previous studies had shown that the substance FR from the plant Ardisia crenata, which is a common houseplant, has an effect on Gq proteins. The researchers therefore hoped to use FR to inhibit many different vasoconstrictors equally. They first tested the substance on isolated pulmonary vessels from mice and demonstrated its effectiveness.

"FR quickly resulted in significant vascular relaxation," points out Seidinger. Subsequent tests on tissue from pigs and human samples confirmed this effect. In experiments on mice suffering from pulmonary hypertension, the researchers eventually showed that treatment with FR alleviated the symptoms and greatly improved the animals' state of health.

"The thickness of the muscle layer around the pulmonary vessels decreased—or didn't even increase in the first place," says Seidinger.

The researchers only observed minor side effects: The blood pressure dropped slightly throughout the body. In fact, this could be beneficial in the treatment of pulmonary hypertension.

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

More information: Alexander Seidinger et al, Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension, EMBO Molecular Medicine (2024). DOI: 10.1038/s44321-024-00096-0

Citation: Active plant substance found to reduce pulmonary hypertension (2024, July 8) retrieved 30 July 2024 from https://medicalxpress.Com/news/2024-07-substance-pulmonary-hypertension.Html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

PAH Risk Scoring Systems Can Also Predict Survival In Pulmonary Hypertension

Risk stratification scoring systems designed for pulmonary arterial hypertension (PAH) that include 3 or 4 strata can also predict survival in patients with non-PAH pulmonary hypertension (PH), according to study findings published in Chest.

Researchers assessed whether risk scores originally developed for PAH had prognostic value in pulmonary hypertension groups 1 to 4. Toward that end, the researchers compared how well several major 3- and 4-strata PAH risk scoring systems predicted PH survival in patients who enrolled in the Pulmonary Vascular Research Institute (PVRI) GoDeep meta-registry.

Patients included for analysis had a right heart catheter-confirmed PH diagnosis from a participating PH expert center and were at least 18 years of age at diagnosis. The analysis included the REVEAL Lite 2 risk score, the REVEAL 2.0 risk score, the European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 risk score, and the COMPERA registry 3-/4-strata risk scores.

The PVRI GoDeep meta-registry had 27,070 patients on October 16, 2023, including 8565 incident and treatment-naïve patients in 15 PH centers. Among the cohort, 3537(41%) patients were diagnosed with group 1 PH, 1807 (21%) had group 2 PH, 1635 (19%) had group 3 PH, and 1586 (19%) patients had group 4 PH. Their median age was 65 (range, 52-74) years, and 39% were male. The median pulmonary arterial pressure was 42 (range, 33-52) mm Hg, and the median pulmonary vascular resistance was 7 (range, 4-11) WU.

"

This comprehensive study with real-world data from 15 PH centers substantially extends our understanding of the predictive power of PAH-designed risk scores, including their potential application in PH patients beyond the PAH group.

All the risk scores predicted survival for patients with incident PH. The REVEAL scores were significantly better than the ESC/ERS risk 2022 score and compared favorably to the COMPERA registry 3-strata risk score. Among patients with REVEAL Lite 2.0 score of 6 or less, the overall 1-, 3-, and 5-year survival rates were 93%, 78%, and 66%, respectively, including patients in all PH groups. Those with higher scores had a significantly worse prognoses.

In univariate Cox regression analysis, significantly increased hazard ratios were confirmed for each point increase in REVEAL 2.0 and REVEAL Lite 2, compared with patients with a total score of 6 points or less. The COMPERA registry 4-strata risk score was able to discriminate between intermediate-low and intermediate-high risk patients and significantly outperformed the ESC/ERS risk 2022 score.

In PH group-based analyses, all included risk scores predicted survival in PH groups 1 to 4. The ESC/ERS 2022 risk score had an uneven distribution with strong predominance of the intermediate risk score group for the 4 PH groups. The COMPERA 4-strata risk score discriminated intermediate-low and intermediate-high patients in all groups. REVEAL scores C-indices in a continuous scoring system were the highest for each individual PH group.

PAH-designed 3- and 4-strata risk scores had predictive power in each subgroup, with strong discrimination of the continuous REVEAL scores and efficacy of the 4-strata risk score to discriminate between intermediate-low and intermediate-high cohorts.

Similar results were observed when dichotomizing the overall PH cohort and each PH group for severe vs nonsevere PH (PVR ≥5 WU and PVR <5 WU).

Limitations include the retrospective study design, the ability to perform only limited subgroup analyses, and possible selection bias.

"This comprehensive study with real-world data from 15 PH centers substantially extends our understanding of the predictive power of PAH-designed risk scores, including their potential application in PH patients beyond the PAH group," the investigators stated.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors' disclosures.

This article originally appeared on Pulmonology Advisor

---