Molecular form and concentration of serum α2-macroglobulin in diabetes

Sci Rep. 2019 Sep 10;9(1):12927. doi: 10.1038/s41598-019-49144-7.

Abstract

α2-Macroglobulin is a highly abundant serum protein involved in the development of atherosclerosis and cardiac hypertrophy. However, its circulating molecular form and exact concentrations in human health/diseases are not known. Blue native-polyacrylamide gel electrophoresis of human serum was used to confirm the native conformation of α2-macroglobulin. We created an enzyme-linked immunosorbent assay suitable for quantifying its circulating molecular form and undertook a cross-sectional study to measure its serum levels in 248 patients with diabetes mellitus and 59 healthy volunteers. The predominant circulating molecular form of α2-macroglobulin was the tetramer, whereas its dimer was detectable in patients with high serum levels of α2-macroglobulin. The serum α2-macroglobulin concentration was not associated with glycated hemoglobin or any other glycemic variable as evaluated from 48-h continuous glucose monitoring, but showed close correlation with left ventricular posterior wall thickness, carotid artery intima-media thickness, urinary albumin:creatinine ratio (ACR) and brachial-ankle pulse wave velocity (baPWV). Multivariate analysis revealed only the ACR and baPWV to be independent variables influencing serum levels of α2-macroglobulin. Thus, an increased ACR and baPWV are associated with higher serum concentrations of α2-macroglobulin, and the latter may contribute to the mechanism by which albuminuria increases the risk of developing cardiovascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Blood Glucose / analysis
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Pregnancy-Associated alpha 2-Macroglobulins / analysis*
  • Pregnancy-Associated alpha 2-Macroglobulins / chemistry*
  • Prognosis

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Pregnancy-Associated alpha 2-Macroglobulins
  • hemoglobin A1c protein, human