Abstract 26: Low Plasma Mir-155 Levels and RhoA Activation Correlates with Small AAA Expansion

Abstract

Introduction: Given increased abdominal imaging studies, the incidental diagnosis and treatment of small AAAs is problematic. Presently, no specific recommendations for medical management can be made other than serial observation. The ras homolog member A (RhoA) signaling cascade is implicated in vascular diseases due to its ability to modulate monocyte endothelial invasion. We sought to investigate the RhoA signaling pathway in AAA expansion, along with an endogenous inhibitor of RhoA, microRNA-155 (miR-155). Hypothesis: We hypothesize that RhoA is activated to enable AAA expansion, but once expanded, miR-155 is called on to inhibit RhoA activation so that the expanded AAA can be stabilized. Methods: Peripheral blood was collected for monocyte and plasma isolation from stable AAA (< 0.1 cm/year) (n=9) and expanding AAA (≥ 0.1 cm/year) (n=10) patients. Rhotekin-RBD assay and western blots were used to assess relative Rho-GTP expression and quantitative PCR for miR-155 detection in blood plasma. T-test and χ2 analysis were used to determine statistical significance. Results: Given limited monocytes, 6 stable and 10 expanding AAA patients were identified for RhoA analysis. Monocytes from expanding AAA patients contained higher active Rho-GTP protein levels compared to stable AAA monocytes (Figure 1a: 1.60±.075 vs 1.20±.088, ρ=.0004). Plasma concentrations of miR-155 were significantly lower in expanding AAA plasma compared to stable AAAs (Figure 1b: -2.17±.95, P=.005). Conclusions: Expanding AAA patients have greater monocyte activation of RhoA and decreased plasma expression of miR-155, when compared to stable AAA patients. The RhoA signaling pathway has altered activation in AAA disease and its regulation may reduce expansion rates and inflammation.