Changes in blood levels of microRNAs may affect CTEPH
Molecules regulate genes involved in producing proteins, like clotting factors
Abnormalities in blood levels of various microRNAs (miRNAs) — small RNA molecules that regulate other genes in protein production — may contribute to the development and progression of chronic thromboembolic pulmonary hypertension (CTEPH), according to a review study.
Particularly, CTEPH patients had high levels of two miRNAs — miR-127 and miR-30a — that are associated with inflammation, vascular remodeling (changes to the arrangement and structure of blood vessels), and dysregulated blood clotting. In contrast, five miRNAs, which could have a protective effect by reducing the formation of blood clots or vascular remodeling, were at lower levels in CTEPH patients than in people without this disease.
“Our findings offer insights into the role of miRNAs in CTEPH and underscore the need for further research to validate these miRNAs as biomarkers or therapeutic targets,” the researchers wrote.
The study, “MicroRNA expression alteration in chronic thromboembolic pulmonary hypertension: A systematic review,” was published in Pulmonary Circulation.
Previous work indicates that miRNAs could be a CTEPH treatment target
A rare type of pulmonary hypertension (PH), CTEPH is caused by the formation of blood clots in the pulmonary arteries, the blood vessels that supply the lungs. PH, overall, is marked by abnormally high pressure in these blood vessels, so that the heart must work harder to pump blood, which can weaken heart muscle.
While specific treatments for CTEPH exist, from pharmaceuticals to treatment approaches, they are not effective for every patient, the researchers, all in Indonesia, noted.
Previous studies indicated that the dysregulation of certain miRNAs may play a role in CTEPH, “suggesting that these molecules may serve as potential biomarkers for diagnosis and targets for therapeutic intervention,” the scientists wrote. However, studies into miRNA levels in CTEPH are scarce and inconsistent, they added.
The team conducted a systematic review of published studies addressing changes in the levels of miRNA molecules in CTEPH patients relative to those levels in individuals without the disease, serving as a control group. A total of nine studies, involving 235 people, were included in the analysis.
Overall, seven miRNAs were found at higher levels, or upregulated, in CTEPH patients compared with controls. Among them, two — miR-665 and miR-3202 — were upregulated in three studies, while the remaining five were higher in one study each.
Specifically, upregulation of miR-655 is associated with a lesser proliferation of vascular smooth muscle cells, a process involved in the vascular remodeling that is a hallmark of PH. Evidence of miR-655’s involvement in CTEPH is conflicting, the investigators noted. They added that miR-655 has a known protective role in CTEPH, so finding it at high levels in patients is “a paradox.”
According to the researchers, “another plausible explanation for this phenomenon is that perhaps the high levels of miR‐665 observed in patients with CTEPH are an adaptive response against disease progression.”
Five of nine protective miRNAs at lower levels in patients’ blood
Two other upregulated miRNAs, miR-127 and miR-30a, previously were associated with CTEPH development. miR-127 is known to promote inflammation and vascular remodeling, while miR-30a is associated with a dysregulation of blood clotting factors — proteins that help the blood to clot — and with heart attacks.
In contrast, nine miRNAs were found at lower levels, or downregulated, in patients. Among those reported in multiple studies were miR-17-5p, miR‐106b‐5p, and miR‐93‐5p.
Among these, five were consistently shown to be protective against CTEPH in previous studies, through several mechanisms. For instance, miR‐20‐a — identified in one study — blocks the activity of tissue factor, another protein involved in blood clotting, while miR‐93‐5p, miR‐106b‐5p, or let-7b ease vascular remodeling.
“From these findings, it could be postulated that miRNAs may play an essential role in the development of CTEPH,” the researchers wrote. “The downstream mechanisms that were identified to be influenced with miRNAs dysregulation are thrombosis [the formation of blood clots] and vascular remodeling.”
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