Invited commentary

Abstract

Microinhibitory RNA (miRNA) were first described by Ambrose et al1Lee R.C. Feinbaum R.L. Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell. 1993; 75: 843-854Abstract Full Text PDF PubMed Scopus (9619) Google Scholar in 1993. They represented an entirely new and important layer of gene regulation. They are naturally occurring short, single-stranded RNA sequences that typically regulate many different genes. It is interesting to note that Andy Fire and Craig Mello received the 2006 Nobel Prize for Medicine for the use of synthetic double-stranded RNA that could inhibit protein production (small-interfering RNA).2Fire A. Xu S. Montgomery M.K. Kostas S.A. Driver S.E. Mello C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.Nature. 1998; 391: 806-811Crossref PubMed Scopus (11712) Google Scholar The discovery of Victor Ambrose is arguably of equal importance. Elegant studies have since demonstrated their role in regulating abdominal aortic aneurysm (AAA).3Maegdefessel L. Azuma J. Toh R. Deng A. Merk D.R. Raiesdana A. et al.MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion.Sci Transl Med. 2012; 4: 122ra22Crossref PubMed Scopus (227) Google Scholar The work presented by Courtois et al takes these findings to another level. By comparing patients whose AAAs showed activity on positron emission tomography (PET) scan against a group of PET-negative AAA patients, the authors have identified a small number of circulating miRNAs that can effectively distinguish between the groups. Finding an accurate systemic biomarker for the presence of AAA or for AAA that are likely to progress to rupture would be an important advance in public health. The study by Courtois et al does not address the issue of identifying a biomarker to find those with AAA. This remains a critical question, because too many patients at risk are not being screened despite the efforts of the Society for Vascular Surgery in promoting aneurysm screening.4Mell M.W. Hlatky M.A. Shreibati J.B. Dalman R.L. Baker L.C. Late diagnosis of abdominal aortic aneurysms substantiates underutilization of abdominal aortic aneurysm screening for medicare beneficiaries.J Vasc Surg. 2013; 57 (1523.e1): 1519-1523Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Significant progress in understanding AAA biology has been made in recent decades. We understand that inflammation drives the pathophysiology. An entirely logical assumption, therefore, is that circulating markers that reflect PET fluorodeoxyglucose activity would identify aneurysms most likely to progress, possibly to rupture. Although the results presented in their study are exciting, we should not get ahead of ourselves as clinicians and scientists. Studying AAA rupture is extremely difficult because small aneurysm rupture is rare, and patients at risk of rupture, based on size, are repaired. Although logical to assume a link between increased PET fluorodeoxyglucose activity and risk of rupture, the data are not there to make this jump. Important questions remain, including whether an aneurysm might show increased activity at one point with regression of the inflammation over time. So how might biomarkers that identify more dangerous AAA be found? The most convincing data would be derived from a carefully studied cohort where aneurysm progression is tracked longitudinally by the best available imaging (computed tomography or magnetic resonance imaging). Showing biomarkers that strongly correlate with growth or, conversely, lack of growth over time would provide the best support for clinical application. The carefully conducted studies by Courtois et al suggest that a panel of miRNAs could prove to be a very useful biomarker in the future for tracking AAA progression. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Circulating microRNAs signature correlates with positive [18F]fluorodeoxyglucose-positron emission tomography in patients with abdominal aortic aneurysmJournal of Vascular SurgeryVol. 67Issue 2PreviewPrediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [18F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography (PET) in AAA was correlated with cellular and molecular alterations involved in wall instability and its potential rupture. Our study aimed at identifying circulating miRNAs correlated with a positive PET that could help discriminate patients at high risk of rupture. Full-Text PDF Open Archive