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P5.2 Quantitative Proteomics Reveal Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes, But Reduced Amounts Among Metformin Users

Abstract

We hypothesized that metformin intake influence the molecular composition of arterial tissue from patients with type 2 diabetes.

We analyzed non-atherosclerotic, internal mammary arteries, gathered at coronary by-pass operations from 30 patients with type 2 diabetes (16 treated with metformin, 14 without), as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual trypsinized extracts of formalin fixed, paraffin embedded tissue. Sections were also analyzed by histology and immunohistochemistry.

We were able to quantitate 129 proteins. The amounts of the basement membrane (BM) component, alpha-1-type IV collagen were increased in patients with diabetes (0.96 +/− 0.05 (non-DM, n=30) vs 1.35 +/− 0.09 (T2DM, n=30), t-test: p = 0.00015, Benjamini-Hochberg correction: p=0.02), as was other BM-components, i.e. laminins and nidogen. The expression of type IV collagen, laminin and other altered proteins were significantly lower among metformin users, compared to patients not treated with metformin (alpha-1-type IV collagen: 1.63 +/− 0.1 (no metformin treatment, n=14)) vs 1.17 +/− 0.10 (metformin treated, n=16) (arb.units)), p=0.013). Patients treated with or without metformin had similar levels of HbA1c, cholesterol and blood pressure.

Accumulation of basement membrane proteins as part of the arteriopathy of type 2 diabetes link the diabetic macro- and micro-angiopathy and provides a molecular substrate for altered functions of the arteries in diabetes, as for example dysfunctional remodeling. Reduced amounts of basement membrane components in metformin treated individuals, despite similar glycemic control, are compatible with the hypothesis that metformin influence the vasculature.

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Preil, S., Kristensen, L., Beck, H. et al. P5.2 Quantitative Proteomics Reveal Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes, But Reduced Amounts Among Metformin Users. Artery Res 8, 143 (2014). https://doi.org/10.1016/j.artres.2014.09.139

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  • DOI: https://doi.org/10.1016/j.artres.2014.09.139