Background-Our aim was to establish a novel model of abdominal aortic aneurysms (AAA) in mice using application of peri-adventitial elastase.

Introduction MicroRNAs (miRs) are noncoding, endogenous RNA molecules that regulate gene expression and play roles in response to vascular injury. Aim The aim of this study was to identify miRs expressed in corporal tissue (CT) and to determine whether miRs demonstrate differential expression in a mouse model of diet-induced erectile dysfunction (ED). Methods RNA was isolated from the CT from control mice and mice with diet-induced ED. A quantifiable miR profiling technique (NanoString) was used to determine the expression of over 600 miRs. Main Outcome Measures Differential expression analysis was performed using a negative binomial regression model for count-based data. Mean expression levels, fold change, and false discovery-corrected P values were determined. Candidate miRs were validated via quantitative polymerase chain reaction (Q-PCR). Results In control mice, NanoString analysis revealed that 181 miRs were expressed above background levels and 5 miRs were expressed at high levels. Diet-induced ED resulted in the up-regulation of 6 miRs and the down-regulation of 65 miRs in the CT compared with mice on control diet. Focusing on the upregulated miRs, we chose five for Q-PCR validation. Of these five, two (miR-151-5p and miR-1937c) demonstrated significance via Q-PCR, whereas the other three (miR-720, miR-1937a, miR-205) trended in the correct direction. Conclusions MiRs may play a significant role in mRNA regulation in CT and specific miRs may be involved in diet-induced vasculogenic ED. Future studies are aimed at determining the mRNA targets of these miRs.

This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Activation of the adenosine 2A receptor (A2AR) reduces inflammation in models of acute injury but contribution in development of chronic abdominal aortic aneurysms (AAAs) is unknown. Elastase perfusion to induce AAA formation in A2AR-knockout (A2ARKO) and C57BL6/J wild-type (WT) mice resulted in nearly 100% larger aneurysms in A2ARKO compared to WT at d 14 (P<0.05), with evidence of greater elastin fragmentation, more immune cell infiltration, and increased matrix metallatoproteinase (MMP) 9 expression (P<0.05). Separately, exogenous A2AR antagonism in elastase-perfused WT mice also resulted in larger aneurysms (P<0.05), while A2AR agonism limited aortic dilatation (P<0.05). Activated Thy-1.2(+) T lymphocytes from WT mice treated in vitro with A2AR antagonist increased cytokine production, and treatment with A2AR agonist decreased cytokine production (P<0.05 for all). Primary activated CD4(+) T lymphocytes from A2ARKO mice exhibited greater chemotaxis (P<0.05). A2AR antagonist increased chemotaxis of activated CD4(+) cells from WT mice in vitro, and A2AR agonist reduced this effect (P<0.05). A2AR activation attenuates AAA formation partly by inhibiting immune cell recruitment and reducing elastin fragmentation. These findings support augmenting A2AR signaling as a putative target for limiting aneurysm formation.

No abstract