Researchers discovered that the expression of circular RNA of silent information regulator factor 2-related enzyme 1 (circ-Sirt1) and sirtuin 1 (SIRT1) was lower in hypoxic rat models of pulmonary arterial hypertension (PAH) compared to nonhypoxic rat models, as published in SAGE Journals.

PAH often manifests as long-term hypoxia with signs of pulmonary vasoconstriction, pulmonary arterial vascular remodeling, and an increase in pulmonary vascular resistance. This eventually leads to right heart failure and death. 

CircRNAs have various biological functions and have been demonstrated to be involved in the pathology of many lung and cardiovascular diseases. They have been linked to pathological processes such as vascular remodeling, vascular cell apoptosis, oxidative stress, and inflammation.


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“However, there are hardly any studies that have explored the relationship between CircRNA and PAH,” Diao and colleagues wrote. They hence decided to conduct a study on hypoxic PAH rat models to investigate the response of circ-Sirt1 and SIRT1 mRNA to hypoxia.

Read more about PAH etiology

They obtained 12 PAH rat models from the Experimental Animal Center of Bengbu Medical College in China. The rats were randomized into 2 groups: one was kept under normoxic conditions, while the other was kept under hypoxic conditions. After 40 days, the rats were euthanized and their tissues were analyzed.

Upon dissection, the researchers reported pulmonary arterial vascular thickening and lumen stenosis in the hypoxic group. In addition, western blot and reverse transcription-polymerase chain reaction analysis revealed a lower expression of circ-Sirt1 and SIRT1 in the hypoxic group compared to the normoxic group.

“Based on this, we speculated that circ-Sirt1 and SIRT1 may be related to PAH,” the researchers wrote. They theorized that circ-Sirt1 regulates SIRT1 mRNA expression and inhibits the proliferation and migration of pulmonary artery smooth muscle cells.

“These results provide a new revelation regarding the molecular mechanism of pulmonary artery vascular remodeling in PAH and may help in the development of new and effective treatment options for PAH,” they concluded.

Reference

Diao W, Liu G, Shi C, et al. Evaluating the effect of circ-Sirt1 on the expression of SIRT1 and its role in pathology of pulmonary hypertensionCell Transplant. Published online February 28, 2022. doi:10.1177/09636897221081479