Diabetes-induced alteration of metal ion levels declines the activity of MMPs to decrease aortic aneurysm risk.

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Metabolic Diseases

Background:

• Diabetes mellitus (DM) is linked to cardiovascular disease risk.
• Diabetic populations paradoxically show reduced aortic aneurysm development.
• Matrix metalloproteinases (MMPs) are implicated in aortic aneurysm pathogenesis.

Purpose of the Study:

• To investigate if DM-induced changes in metal ion levels decrease MMP activity, thereby reducing aortic aneurysm risk.
• To explore the mechanistic link between diabetes, metal ions, MMPs, and aortic aneurysms.

Main Methods:

• Cultured vascular smooth muscle cells (VSMCs) and macrophages under high glucose conditions.
• Established a mouse model of streptozotocin-induced diabetes with abdominal aortic aneurysm.
• Administered dietary zinc supplementation to diabetic mice.
• Analyzed serum metal ion levels (Zn2+, Mg2+), aneurysm size, gene expression (fibronectin, CTGF), and MMP activity (MMP2, MMP9).
• Correlated clinical data of DM, serum Zn2+ levels, and aortic aneurysm risk.

Main Results:

• High glucose increased fibronectin and CTGF in VSMCs, and MMP2/MMP9 in macrophages.
• Diabetic mice exhibited lower serum Zn2+ and Mg2+, smaller aneurysms, and higher fibronectin/CTGF expression.
• Dietary zinc supplementation reversed these effects in diabetic mice.
• Enzymatic activity of MMP2 was modulated by Zn2+ and Mg2+ concentrations.
• Clinical data confirmed correlations between DM, serum Zn2+ levels, and aortic aneurysm risk.

Conclusions:

• DM-induced alterations in metal ion levels, particularly zinc, reduce MMP activity.
• This reduction in MMP activity appears to negate aortic aneurysm development in diabetic individuals.
• Findings offer novel mechanistic insights and a potential therapeutic strategy for aortic aneurysms.