RUNX1 gene may serve as biomarker for right heart failure in PAH
Study: It could be a target for future experimental therapies
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The activity of a gene called RUNX1 may serve as a biological marker of processes that can lead to right heart failure in pulmonary arterial hypertension (PAH), a study reports.
Progressive decline of the right ventricle, the chamber of the heart that pumps blood to the lungs, is a serious complication of PAH. The research team examined genes in right ventricular tissue from people with PAH and severe right ventricular failure. They found abnormally high levels of RUNX1 activity compared to control tissue.
“These results suggest that RUNX1 may be involved in [right ventricular] failure in the context of PAH through inflammation and could serve as a potential biomarker for this condition,” researchers wrote. The gene could also be a target for future experimental therapies targeting PAH and right ventricular failure, they hypothesized.
The study, “Identification of RUNX1 as a Biomarker for Right Ventricular Remodeling in Pulmonary Arterial Hypertension Using WGCNA,” was published in the journal Pulmonary Circulation.
Cardiac remodeling a potential therapeutic target in PAH
In pulmonary hypertension (PH), the blood pressure in the pulmonary arteries, which supply blood to the lungs, becomes elevated. PAH is a rare type of PH characterized by narrowing of the pulmonary arteries. This restricts blood flow, which can force the heart to work harder to deliver blood to the lungs.
Initially, the hearts of people with PAH may be able to compensate for this extra work. As the problems continue, however, a process called cardiac remodeling begins to restructure the heart, leading to a decline in heart function. This is referred to as decompensation.
Targeting cardiac remodeling could, in theory, help slow or prevent decompensation and reductions in heart function. However, scientists don’t entirely understand how or why the remodeling process occurs.
“Due to the unclear molecular mechanisms underlying [right ventricular] remodeling, therapeutic strategies remain limited, contributing to the poor prognosis observed in PAH patients,” the research team wrote. “Therefore, early identification of RV remodeling in PAH and exploration of its underlying mechanisms are of significant clinical importance.”
RUNX1 identified as strongest biomarker candidate
In the current study, the team investigated gene activity in healthy and decompensated right ventricular tissue. Their data set included tissue samples from the hearts of 13 control donors without PAH and 13 people with PAH and signs of right ventricular decompensation.
The analysis revealed 2,384 genes with significantly different activity patterns in control versus decompensated tissue. Using computational techniques, the researchers split these genes into groups with interrelated activity patterns and functions. They then identified hubs — genes that had the most connections to other genes in the same group. Hub genes may represent key differences between the control and decompensated tissue.
Three genes emerged as potential markers of right ventricular decompensation. By cross-checking these genes against a second data set of right ventricle tissue, the team identified RUNX1 as the strongest candidate.
Although RUNX1 is expressed at relatively low levels in the normal adult heart, its expression increases under stress conditions and is closely associated with adverse cardiac remodeling.
Experiments in a rat model of PAH supported RUNX1 as a possible biomarker of right ventricular remodeling. The PAH rats showed elevated RUNX1 activity (expression) in decompensated heart tissue compared with healthy animals.
RUNX1 helps regulate the life cycle of heart cells, with implications for cell survival.
“Although RUNX1 is expressed at relatively low levels in the normal adult heart, its expression increases under stress conditions and is closely associated with adverse cardiac remodeling,” the researchers wrote.
Specifically, excessive RUNX1 activity may promote inflammatory pathways, contributing to heart failure and remodeling. The researchers suggested that RUNX1 might therefore be a useful biomarker of this remodeling and decompensation. Future studies could also use RUNX1 as a therapeutic target to decrease remodeling.
However, the datasets in this study were relatively small, so additional experiments will be needed to continue exploring these hypotheses.
“Further validation with more samples is needed to confirm RUNX1 as a specific biomarker for [right ventricular] failure under the context of PAH,” the team wrote.
