Diabetes Reduces Severity of Aortic Aneurysms Depending on the Presence of Cell Division Autoantigen 1 (CDA1)

Area of Science:

• Vascular Biology
• Metabolic Disease Research

Background:

• Diabetes mellitus is a known negative risk factor for aortic aneurysm development, but the mechanisms remain unclear.
• Previous research indicated cell division autoantigen 1 (CDA1) is upregulated in diabetes and enhances transforming growth factor-β (TGF-β) signaling.

Purpose of the Study:

• To investigate the hypothesis that CDA1 mediates the protective effect of diabetes against aortic aneurysms.
• To elucidate the role of CDA1 in the context of diabetes-induced changes in aortic tissue.

Main Methods:

• Diabetic models were created using wild-type, CDA1 knockout (KO), apolipoprotein E (ApoE) KO, and CDA1/ApoE double-KO (dKO) mice.
• Aneurysm formation was assessed, alongside analysis of TGF-β signaling, collagen expression, macrophage infiltration, and matrix metalloproteinase 12 (MMP-12) activity.
• Angiotensin II-induced aneurysm models were used to evaluate the impact of diabetes and CDA1 deletion on aortic rupture and expansion.

Main Results:

• Diabetic dKO mice showed a 40% incidence of aortic aneurysms, unlike diabetic wild-type and ApoE KO mice.
• Aneurysms in dKO mice were characterized by attenuated TGF-β signaling, reduced collagen, increased macrophages, and elevated MMP-12.
• Diabetes reduced aortic rupture and expansion in angiotensin II models, but these protective effects were abolished in dKO mice.
• Human abdominal aortic aneurysm biopsies revealed a significant downregulation of vascular CDA1 expression.

Conclusions:

• Vascular CDA1 is upregulated in diabetes and plays a critical role in conferring protection against aortic aneurysm formation.
• CDA1 deletion in diabetic mice abrogates the protective effects of diabetes, leading to increased susceptibility to aneurysms.
• These findings identify CDA1 as a key molecular player in the interplay between diabetes and aortic aneurysm pathogenesis.