Genetic deficiency of protein inhibitor of activated STAT3 suppresses experimental abdominal aortic aneurysms.

AIM

Signal transducer and activator of transcription (STAT) signaling is critical for the pathogenesis of abdominal aortic aneurysms (AAAs). Though protein inhibitor of activated STAT3 (PIAS3) negatively modulates STAT3 activity, but its role in AAA disease remains undefined.

METHOD

AAAs were induced in PIAS3 deficient (PIAS3) and wild type (PIAS3) male mice transient intra-aortic elastase infusion. AAAs were assessed by measurements of infrarenal aortic external diameters prior to (day 0) and 14 days after elastase infusion. Characteristic aneurysmal pathologies were evaluated by histopathology.

RESULTS

Fourteen days following elastase infusion, aneurysmal aortic diameter was reduced by an approximately 50% in PIAS3 as compared to PIAS3 mice. On histological analyses, PIAS3 mice showed less medial elastin degradation (media score: 2.5) and smooth muscle cell loss (media score: 3.0) than those in PIAS3 mice (media score: 4 for both elastin and SMC destruction). Aortic wall leukocyte accumulation including macrophages, CD4 T cells, CD8 T cells and B cells as well as mural neovessel formation were significantly reduced in PIAS3 as compared to PIAS3 mice. Additionally, PIAS3 deficiency also downregulated the expression levels of matrix metalloproteinases 2 and 9 by 61% and 70%, respectively, in aneurysmal lesion.

CONCLUSION

PIAS3 deficiency ameliorated experimental AAAs in conjunction with reduced medial elastin degradation and smooth muscle cell depletion, mural leukocyte accumulation and angiogenesis.