Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

Int J Mol Sci. 2015 May 18;16(5):11276-93. doi: 10.3390/ijms160511276.

Abstract

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.

Keywords: abdominal aortic aneurysm; adventitial tertiary lymphoid organs; laser microdissection; microRNA; quantitative RT-PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adventitia / metabolism*
  • Adventitia / physiopathology
  • Aged
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Aneurysm, Abdominal / complications
  • Aortic Aneurysm, Abdominal / genetics
  • Aortic Aneurysm, Abdominal / pathology*
  • Biomarkers / metabolism
  • Coronary Disease / etiology
  • Female
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / metabolism
  • Male
  • MicroRNAs / isolation & purification
  • MicroRNAs / metabolism*
  • Middle Aged
  • Peripheral Arterial Disease / genetics
  • Peripheral Arterial Disease / pathology
  • Real-Time Polymerase Chain Reaction
  • Risk Factors

Substances

  • Biomarkers
  • MicroRNAs