Molecular form and concentration of serum α2-macroglobulin in diabetes

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.

Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

“…In human blood, its function is related to the regulation of the immune system, the control of the blood coagulation system and the suppression of the fibrinolytic system [ 72 ]. α2M is a highly abundant serum protein involved in the development of atherosclerosis; however, its circulating concentrations in human health/diseases are not exactly known [ 73 ]. The A2M gene expression modulates the severity and extent of atherosclerosis [ 74 ].…”

Coagulatory Defects in Type-1 and Type-2 Diabetes

“…In contrast, in T1DM, the PAI-1 concentration is reduced [39]. The concentration of other inhibitors of fibrinolysis, including thrombin-activatable fibrinolysis inhibitor [40,41] and α2-macroglobulin [32,42], are also elevated in both T1DM and T2DM, while the α2-antiplasmin concentration is elevated in T2DM [19], but in T1DM it has been reported to be elevated in two studies [19,43], but reduced in another [22]. Again, the origin of this difference is not known but could be due to differences in methodology or to different stages of progression of the disease in the individuals studied.…”

Suprabasin-derived bioactive peptides identified by plasma peptidomics

“…Western blotting was performed essentially as described 53 , 59 . Confluent HAoSMCs (1.2 × 10 6 cells) deprived of serum for 16 h were incubated with SBSN_HUMAN[225–237] or SBSN_HUMAN[243–259] for the indicated time, washed three times with phosphate-buffered saline (PBS) and solubilized in RIPA Lysis and Extraction Buffer (Thermo Fisher Scientific) containing 10 μM protein inhibitors (Thermo Fisher Scientific).…”