The long non-coding RNA LIRIL2R level in essential arterial hypertension: possible association with the FOXP3 mRNA splicing isoforms

Abstract

The aim of the study was to evaluate the content of the LIRIL2R of the long non-coding RNA (lncRNA) in peripheral blood leukocytes (PBL) and its relationship with interleukin 2 (IL-2) levels and the number of the FOXP3 mRNA splicing isoforms in patients with essential arterial hypertension (EAH). Design and methods. The study included 25 healthy individuals and 17 patients diagnosed with EAH (stages I–II) before antihypertensive therapy and 21 patients taking cardioselective β-blockers (metoprolol 25 mg/day or bisoprolol 5– 10 mg/day) for more than a year. The level of gene transcripts was assessed by real-time polymerase chain reaction (PCR). The content of IL-2 was determined by the ELISA. Statistical processing of the results was carried out in the Statgraphics Centurion XVI (version 16.1.11) and the GraphPad Prism v. 7 software packages (USA). Results . The relative level of the LIRIL2R transcripts in PBL of EAH patients (a group of patients before antihypertensive therapy and a group of patients taking cardioselective beta-blockers) was higher than in healthy people (p < 0,05). The relative transcript content of the full-length form of the FOXP3 mRNA ( FOXP3FL ), the isoform lacking exon 2 ( FOXP3Δ2 ), and the form with included exon 2 ( FOXP3e2 ) was higher in PBL of patients without antihypertensive therapy when compared with healthy individuals and patients on therapy (p < 0,05). In PBL of EAH patients who had not previously taken antihypertensive drugs, the FOXP3Δ2 transcripts were predominant ( FOXP3Δ2/FOXP3e2 – 1,3). In PBL of healthy individuals and patients on therapy, there were more transcripts with included exon 2 ( FOXP3Δ2/FOXP3e2 was 0,4 and 0,12, respectively). In the group of healthy individuals, the LIRIL2R level in PBL negatively correlated with the amount of the FOXP3Δ2 transcripts (r = −0,63; p = 0,029). The IL-2 content in the plasma of EAH patients before antihypertensive therapy was significantly higher than in patients taking metoprolol or bisoprolol, and in healthy individuals (p < 0,05). A relationship between the amount of the LIRIL2R transcripts and the IL-2 content in the plasma of EAH patients without antihypertensive therapy was found (r = 0,85; p = 0,024). In the same group of subjects, the level of the LIRIL2R expression positively correlated with the relative content of the FOXP3Δ2 and FOXP3e2 transcripts (r = 0,99; p = 0,027 in both cases). The LIRIL2R levels positively correlated with soluble form of the intercellular adhesion molecule (sICAM) (r = 0,528; p = 0,013) and malondialdehyde (MDA) (r = 0,548; p = 0,004) levels. Conclusion. The increased LIRIL2R transcript levels in PBL of EAH patients are associated with a change in the ratio of alternatively spliced forms of the FOXP3 gene mRNA and an increase in the levels of sICAM and MDA, indicating its likely involvement in the regulation of inflammation in EAH.