disruption, and how these correlate with endogenous TGF‐β signaling. Methods: Rat aortic SMCs were cultured with IL1β+ or TNF‐α alone (0 and100 ng/ml) and together (50 ng/ml each) over 4–120 h and over 22 days. Based on an initial WNT PCR array, we further screened for Wnts 1, 3, 4, 5A, 7A, MMPs 2, 7, 9 and 24; TIMPS 1–4, TGF‐β; and matrix genes elastin, collagen, LOX, and fibrillin. TCF activation was studied through Topflash/Fopflash ratio analysis. Western blots were performed for select proteins and TEM used to gauge de novo elastic matrix deposition and quality at 22 days. Results: Bootstrapping analysis showed that IL1β+TNF‐α suppressed canonical Wnts (1,3A,4) and greatly enhanced non-canonical Wnts (5A,7A), gradually suppressing TGF-β. These temporally coincided with exponential increases in MMPs 2 and 9 mRNA and protein and elastin gene down-regulation, reflected in a sporadic, nonfibrillar elastic matrix. Conclusions: Our results suggest that elastin and cell homeostasis initially maintained by the canonical Wnts and TGF-β is perturbed by cytokine-activation of Wnts 5A and 7A resulting in enhanced disruption and suppressed regeneration of elastin matrix. The results suggest a potential mechanistic target for therapy to concurrently reverse both these effects to stabilize AAAs.