| Authors |
Li J, Huynh P, Dai A, Wu T, Tu Y, Chow B, Kiriazis H, Du XJ, Bach LA,
Wilkinson-Berka JL, Biros E, Walker P, Nataatmadja M, West M, Golledge J, Allen
TJ, Cooper ME, Chai Z
|
| Submitted By |
Zhonglin Chai on 1/16/2018 |
| Status |
Published |
| Journal |
Diabetes |
| Year |
2018 |
| Date Published |
1/1/2018 |
| Volume : Pages |
Not Specified : Not Specified |
| PubMed Reference |
|
| Abstract |
Diabetes is a negative risk factor for aortic aneurysm, but the underlying
explanation for this phenomenon is unknown. We have previously demonstrated that
Cell Division Autoantigen 1 (CDA1), which enhances TGF-脽 signaling, is
upregulated in diabetes. We hypothesized that CDA1 plays a key role in
conferring the protective effect of diabetes against aortic aneurysms. Male
wildtype, CDA1 knockout, Apolipoprotein E (ApoE) knockout and CDA1/ApoE double
knockout (dKO) mice were rendered diabetic. Whereas aneurysms were not observed
in diabetic ApoE knockout and wildtype mice, 40% of diabetic dKO mice developed
aortic aneurysms. These aneurysms were associated with attenuated aortic TGF-脽
signaling, reduced expression of various collagens as well as increased aortic
macrophage infiltration and matrix metalloproteinase12 expression. In the well
characterized model of angiotensin II (AngII) induced aneurysm formation,
concomitant diabetes reduced fatal aortic rupture and attenuated suprarenal
aortic expansion, changes not seen in dKO mice. Furthermore, aortic CDA1
expression was downregulated ~70% within biopsies from human abdominal aortic
aneurysms. The identification that diabetes is associated with upregulation of
vascular CDA1 and that CDA1 deletion in diabetic mice promotes aneurysm
formation provides evidence that CDA1 plays a role in diabetes to reduce
susceptibility to aneurysm formation.
|
|
|