Abstract Body: Background: Tripartite motif containing 59 (TRIM59) functions as an E3 ubiquitin ligase contributing to host immune responses including innate and adaptive immunity. This study investigated the influence of myeloid cell TRIM59 deletion on experimental abdominal aortic aneurysms (AAAs).
Methods: Nine- to ten-week-old male, myeloid cell-specific TRIM59 deficient (Lysozyme 2 Cre⁺/TRIM59 flox^+/+, CKO) and TRIM59 flox^+/+ (wild type, WT) mice were used in all experiments. Experimental AAAs were induced in all mice by transient intra-infrarenal aortic infusion of porcine pancreatic elastase. Experimental AAA progression was assessed via serial in vivo infrarenal ultrasonographic aortic diameter measurements and histopathologic analysis at sacrifice.
Results: Major findings are summarized in the Figure. On days 7 and 14 following elastase infusion, aortic diameters were significantly larger in CKO than those in WT mice. On histological analysis, elastin degradation was enhanced in CKO mice with a trend toward aortic macrophage accumulation. Aortic accumulation of CD4⁺ and CD8⁺ T cells and B220⁺ B cells, as well as mural neoangiogenesis (identified by CD31⁺ antibody staining) were all more prominent in CKO mice. No difference in α actin-positive aortic medial smooth muscle cell depletion was noted between strains.
Conclusions: Deficiency of myeloid cell TRIM59 augments progression of experimental AAAs.