MicroRNA-206, IL-4, IL-13, and INF-γ levels in lung tissue and plasma are increased by the stimulation of particulate matter with a diameter of ≤2.5μm, and are associated with the poor prognosis of asthma induced pulmonary arterial hypertension patients

Clin Exp Hypertens. 2021 Feb 17;43(2):181-188. doi: 10.1080/10641963.2020.1836192. Epub 2020 Oct 21.

Abstract

Background: This study aimed to explore the prognostic value of particulate matter with a diameter of ≤2.5 μm (PM2.5)-related microRNA-206 combined with interleukin (IL)-4, IL-13 and interferon-γ (INF-γ) in asthma induced pulmonary arterial hypertension (PAH).

Methods: Fifty SPF BALB/c mice were divided into 5 groups: control group, asthma + PAH group, low-toxic asthma + PAH group, moderately-exposed asthma + PAH group, highly-exposed asthma + PAH group. Differences of microRNA-206, IL-4, IL-13, and INF-γ expression in lung tissue and plasma were detected. A total of 98 patients with asthma induced PAH and 98 healthy persons were collected. Patients were followed up for 12 months.

Results: Based on microarray analyses, we found that microRNA-206 may be involved in asthma induced PAH stimulated by PM2.5. Compared with healthy people, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in asthma induced PAH patients were significantly higher (P< .05). Compared with survivors, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in non-survivors were significantly higher (P< .05). Survival analyses showed that compared with low microRNA-206, low IL-4, low IL-13 and low INF-γ groups, survival rate of patients in high microRNA-206 (χ2 = 4.864, P= .013), high IL-4 (χ2 = 3.774, P= .038), high IL-13 (χ2 = 8.375, P< .001) and high INF-γ groups (χ2 = 9.007, P< .001) were significantly reduced. Established prognostic evaluation model was built and the estimated probability was 0.473. Compared with estimated probability ≤ 0.473, survival rate of patients in estimated probability> 0.473 was significantly reduced (χ2 = 17.377, P< .001).

Conclusion: Current model combining plasma microRNA-206, IL-4, IL-13, and INF-γ has potential significance for prognosis of asthma induced PAH.

Keywords: PM2.5; Pulmonary arterial hypertension; asthma; inflammatory; prognosis.

MeSH terms

  • Animals
  • Asthma* / complications
  • Asthma* / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Interferon-gamma* / analysis
  • Interferon-gamma* / blood
  • Interleukin-13* / analysis
  • Interleukin-13* / blood
  • Interleukin-4* / analysis
  • Interleukin-4* / blood
  • Lung / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs* / analysis
  • MicroRNAs* / blood
  • Middle Aged
  • Particulate Matter* / adverse effects
  • Particulate Matter* / analysis
  • Prognosis
  • Pulmonary Arterial Hypertension* / diagnosis
  • Pulmonary Arterial Hypertension* / etiology
  • Pulmonary Arterial Hypertension* / metabolism

Substances

  • Interleukin-13
  • MIRN206 microRNA, human
  • MicroRNAs
  • Mirn206 microRNA, mouse
  • Particulate Matter
  • Interleukin-4
  • Interferon-gamma