A study conducted in an animal model of pulmonary hypertension (PH) which measured levels of microRNAs (miRNA) — small molecules that seem to inhibit the activity and production of other molecules — may provide a new understanding of disease causes. The report, “Reversal of MicroRNA Dysregulation in an Animal Model of Pulmonary Hypertension,“ appeared on Jan. 27, 2016, in the journal PLoS One.
PH refers to high blood pressure in the lungs, and several different types of medical conditions can cause the disease. It worsens over time and can be fatal, since pressure in the lung arteries strain the heart. PH currently has no cure, but medications like vasodilators help to control its symptoms, although they cannot halt disease progression.
In past studies, scientists have measured abnormal levels of miRNAs both in humans with the disease and in animal models of PH.
A team led by Igor Gubrij at the Central Arkansas Veterans Healthcare System, in Little Rock, Arkansas, studied a rat model of PH, in which the animals were given monocrotaline (MCT) to induce PH symptoms. Researchers measured miRNA levels, and also assessed whether using an inhibitor called antagomiR to block a specific miRNA, called miRNA-223, reduced PH symptoms. Finally, they measured miRNAs in PH rats that were also genetically altered to overproduce human prostacyclin synthase, which has been previously shown to reduce PH.
The scientists found that specific miRNAs increased in the PH animal model while others seemed to decline, noting “MiRs 17, 21, and 223 were consistently upregulated, whereas miRs 126, 145, 150, 204, 424, and 503 were downregulated in MCT PAH as compared to [normal animals].” However, blocking miRNA-223 did not have affect PH symptoms.
In their report, the investigators wrote that “[i]nhibition of miR-223 did not attenuate MCT PAH, whereas human prostacyclin synthase over-expression restored miRNA levels in MCT PAH to levels detected in naïve rats.”
The study suggests that specific miRNAs may contribute to PH, although targeting miRNA-223 does not seem to have any impact. Future studies may concentrate on the effects of other miRNAs on PH symptoms. In addition, prostacyclin synthase could be a potential treatment for PH, but research taking it beyond animal studies is first necessary.
“These data suggest that targeting of specific miRNAs or groups of miRNAs may identify which signaling pathways are important for development and treatment of PAH,” the researchers concluded. “The stable and/or protected release of miRNAs into plasma also presents an opportunity to develop single miRNAs or panels of miRNAs as biomarkers for this very complex disease.”