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

Han Nie1, Zi-Sheng Huang2, Geng Liu1

  • 1Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan; Department of Stem Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Life Sciences
|November 16, 2024
PubMed
Abstract

Insights

Diabetes mellitus (DM) lowers aortic aneurysm risk by altering metal ion levels, which reduces matrix metalloproteinase (MMP) activity. Zinc supplementation in diabetic mice normalized these changes, suggesting a therapeutic strategy for aortic aneurysms.

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.
Keywords:
Aortic aneurysmDiabetes mellitusMMPs activityMetal ions level

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