Study Points to TXNRD1 Protein as Potential Diagnostic Marker in IPAH
Levels of the protein TXNRD1 are reduced in the blood of people with idiopathic pulmonary arterial hypertension (IPAH), suggesting it may be useful as a potential diagnostic marker or treatment target in IPAH, according to a new study.
“This study is the first report to prove that TXNRD1 may be used as a clinical predictive molecule and potential therapeutic target for IPAH,” its researchers wrote.
The study, “Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension,” was published in Frontiers in Medicine.
Scientists from Xiangya Hospital in China analyzed gene activity data from four previously published datasets, covering 65 people with IPAH and 63 controls without the disease. From these data, the researchers looked for differentially expressed genes, or DEGs — genes that were expressed at significantly higher or lower levels in the patients, compared to controls.
The analysis revealed 169 DEGs across all the datasets. Further investigation indicated these genes play roles in antioxidant and antibacterial responses, as well as carbon metabolism.
“Results indicated that the robust DEGs were significantly enriched in PAH-related biological processes,” the scientists wrote.
The researchers then conducted additional validation analyses, as well as more detailed analyses of how various genes, and the proteins they encode, are likely to interact. From these, they zeroed in on TXNRD1 for further investigation.
The TXNRD1 protein, encoded by a gene with the same name, is known to play a role in detoxifying reactive oxygen species (ROS), molecules produced as by-products of cellular activities that drive a type of cellular damage called oxidative stress.
Tests of blood samples from nine people with IPAH and 13 controls showed TXNDR1 levels were significantly lower among the IPAH patients.
Among the patients, lower levels of TXNDR1 were statistically correlated with higher mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), suggesting greater blood pressure in the lungs’ vessels. TXNDR1 levels did not correlate with the distance participants could walk in six minutes or with levels of a marker of heart damage called NT-proBNP.
“Our experimental results revealed for the first time that serum [blood] TXNRD1 of IPAH patients was lower than healthy controls and negatively correlated with mPAP and PVR, which suggested TXNRD1 could be a potential diagnostic marker for IPAH,” the researchers said.
The researchers also found that TXNDR1 levels were reduced in the lungs of rats in a model of pulmonary hypertension induced with the chemical monocrotaline.
In cell experiments done with pulmonary artery smooth muscle cells (PASMCs), which line the lung’s blood vessels, reducing TXNDR1 levels led to increased cell growth and migration, along with resistance to programmed cell death or apoptosis — all of which are hallmarks of PASMCs in pulmonary hypertension.
The researchers speculated that TXNRD1’s known role in regulating ROS may help explain these effects.
“Since TXNRD is closely related to ROS production, we speculate based on our findings that the decreased expression of TXNRD1 increases the production of ROS to a certain extent, which can promote the proliferation of PASMC,” they wrote, noting that their hypothesis required more research. The researchers also noted that their study is limited by its small human sample size and that only one animal model was used.