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.
Highlights
Abdominal aortic aneurysm (AAA) is a complex vascular disease and represents a public health care problem, responsible for more than 12,217 deaths in the United States in 2009 [1]
This study aimed first to determine the distribution of inflammatory cells in the different layers of human AAA in order to determine the presence of B/T cell aggregates, which have been described as precursor of adventitial tertiary lymphoid organs (ATLOs) [16]
We looked for the presence and distribution of the inflammatory cells in human AAA, bearing in mind that surgical specimens of human AAA collected from patients undergoing open surgery represent an advanced stage of the disease
Summary
Abdominal aortic aneurysm (AAA) is a complex vascular disease and represents a public health care problem, responsible for more than 12,217 deaths in the United States in 2009 [1]. This high mortality is largely due to the asymptomatic progression before rupture in most AAA patients and, has enhanced the interest for the search for biomarkers that can be detected in blood, facilitating systemic screening of the population at risk [2]. MiRNAs, which are small non-coding RNAs, have recently been shown to be molecular markers because of their role in transcriptional and posttranscriptional regulation [3] Their stability in plasma enhances their potential as biomarkers [4]. Five miRNAs (miR-181a*, miR-146a, miR-21, miR-331-3p and miR-204) were shown to be differentially expressed in the human aneurysmal wall when compared to control human aorta [5]
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