Abstract
MicroRNAs (miRNAs) have been identified as transcriptional and posttranscriptional inhibitors of gene expression, thought to “fine tune” the translational output of their target mRNAs. Recently, they have received much attention regarding their suitability as biomarkers for disease. Our goal was to explore the diagnostic and prognostic value of miRNAs in abdominal aortic aneurysms (AAAs), a disease for which currently no established biomarker exists. Using a PCR-based array platform, we profiled the 168 most abundant blood miRNAs in 20 patient plasma samples with AAA disease, undergoing surgical repair of their enlarged aorta vs. 20 samples from an age, risk factor, and medication matched control group without aneurysm. We were able to identify a total number of 12 miRNAs being significantly altered in diseased patient samples as compared to controls. We further investigated these 12 miRNAs in plasma (as well as in aortic tissue) from apoE-/- mice with angiotensinII (AngII)-infusion induced AAAs, enabling us to discover a potential prognostic value of miRNAs being released into circulation. Indeed we were able to detect that the expression of 4 out of the 12 miRNAs (miRs-126 and -668 both increased; miRs-24 and -210 both decreased), was substantially modified in plasma samples drawn from mice with AAA immediately before rupture occurred between days 10 and 14 after AngII pump implantation compared to mice with AAA that did not rupture for the remainder of study (28 days), as well as saline-infused controls. Importantly, the expression of miRs-24 and -126 appeared also significantly different in plasma samples from patients with ruptured AAAs (n=7) compared to patients with non-ruptured AAAs (abdominal aortic diameter between 55-78 mm; n=7) and un-diseased controls (n=7). The present study explores the diagnostic and prognostic biomarker potential of miRNAs being released into circulation during initiation, propagation, and ultimately rupture of AAA disease in mice and humans. The identification of miRs-24, -126, -210, and -663 potentially offers great prognostic value to determine which patients present with an increased risk of AAA rupture.
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