Abstract 108: Diagnostic and Prognostic Biomarker Potential of miR-24 in Abdominal Aortic Aneurysm Disease and Rupture

Abstract

MicroRNAs (miRNAs) have lately received much attention regarding their suitability and feasibility as biomarkers for cardiovascular diseases. Aim of this current study was to explore the diagnostic and prognostic value of detecting circulating levels of miRNAs in abdominal aortic aneurysms (AAAs). Using a PCR-based array, 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 a matched screening cohort without aneurysm. We were able to identify a total number of 12 miRNAs that were significantly altered in diseased patient samples as compared to controls. Next we investigated these 12 miRNAs in plasma from ApoE-/- mice with angiotensinII (AngII)-infusion induced AAAs, in order to determine the 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 altered in plasma samples drawn from AAA mice 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. The expression of miR-24 was furthermore significantly different in plasma samples from human patients with acutely ruptured AAAs (n=7) compared to patients with non-ruptured AAAs (AA diameter between 55-78 mm; n=7) undergoing surgical repair, as well as un-diseased controls (n=7). Using the AngII model, as well as the elastase infusion model, we were able to show that overexpression of miR-24 protects from aneurysm progression as well as aortic rupture (in the AngII model) by repressing the expression of its target gene chitinase3-like1 (Chi3l1), which regulates macrophage survival and cytokine release in expanding murine AAAs. The present study explores the biomarker potential of miRNAs being released into circulation during initiation, propagation, and ultimately rupture of AAA disease in mice and humans. The identification of miR-24 potentially offers prognostic value to determine which patients present with increased risk of rapid AAA expansion and subsequent rupture.