Reciprocal association of serum Mac-2 binding protein and HDL-cholesterol concentrations.

BACKGROUND: Mac-2 binding protein (Mac-2BP) is used as a serum biomarker of nonalcoholic steatohepatitis, considered to be a liver phenotype of metabolic syndrome (MetS). In this study, we investigated the serum Mac-2BP concentrations-correlated MetS-related clinical parameters in vivo, and the underlying mechanism in vitro. MATERIALS & METHODS: We enrolled 54 healthy Japanese men who underwent health examination at Osaka University Health Care Center in this study. Physical and serum biochemical parameters were obtained from all the subjects. In the cultured HepG2 cells, the effects of interferon (IFN)-γ on the expression of Mac-2BP, apolipoprotein (apo) A-I, and ATP binding cassette transporter A1 (ABCA1) were studied. RESULTS: Serum Mac-2BP concentrations correlated negatively with HDL-C, and positively with body mass index and systolic blood pressure in univariate analysis. These results suggested the association between Mac-2BP and MetS, although none of these 3 parameters had significant correlation with serum Mac-2BP concentrations in multivariate analysis. In HepG2 cells, IFN-γ stimulation resulted in the increased Mac-2BP and the decreased ABCA1 and apo A-I mRNA concentrations, while Mac-2BP had no effects on ABCA1 and apo A-I concentrations. CONCLUSIONS: The serum Mac-2BP concentrations are negatively correlated with HDL-C concentrations in healthy subjects, as a result of chronic inflammation.

Marked elevation of serum M2BP-adiponectin complex in men with coronary artery disease.

BACKGROUND AND AIMS: Adiponectin (APN) is an adipocyte-derived bioactive molecule with anti-diabetic and anti-atherogenic properties. Although the anti-diabetic effects of APN are mediated by AdipoR1 and AdipoR2, the anti-atherogenic mechanisms of APN remain unclear. The aim of this study was to determine the serum molecule inhibiting APN functions. METHODS AND RESULTS: By immunoprecipitation with an anti-APN antibody and mass spectrometry, we identified Mac-2 binding protein (M2BP) as a novel serum APN-binding protein. The association of M2BP and APN was confirmed using reconstituted proteins in vitro. Serum M2BP-APN complex levels were markedly higher in male patients with coronary artery disease (CAD) than in healthy subjects. M2BP abrogated the suppressive effects of APN on tumour necrosis factor (TNF)-α-induced inflammation in vascular endothelial cells. CONCLUSIONS: The increment of serum M2BP-APN complex could be a novel risk factor for CAD, through the abolishment of the anti-atherogenic effects of APN.

E-selectin ligand-1 (ESL-1) is a novel adiponectin binding protein on cell adhesion.

BACKGROUND: Adiponectin (APN) is an adipocyte-derived bioactive molecule with anti-diabetic and anti-atherogenic properties. Although anti-diabetic effects are mostly mediated by the adiponectin receptors AdipoR1 and AdipoR2, the anti-atherogenic mechanisms have not been fully elucidated. METHODS AND RESULTS: In this study, we identified E-selectin ligand (ESL)-1 as a novel APN-binding protein by mass spectrometry analysis of HepG2 cell-derived immunoprecipitant with an anti-APN antibody. Cell adhesion assays using fluorescence-labelled monocyte cell line THP-1 cells and human umbilical vein endothelial cells (HUVECs) revealed that APN-pre-treated THP-1 cells had reduced binding ability to HUVECs. This APN-mediated suppressive effect on monocyte binding to endothelial cells was partially abrogated by targeting ESL-1 with shRNA in THP-1 cells. In addition, serial mutagenesis analysis disclosed that five extracellular amino acids close to the N-terminus of ESL-1 were essential for binding with APN. CONCLUSION: Our results highlight the fact that interaction between APN and ESL-1 could provide a fundamental mechanism underlying the anti-atherogenic properties of APN.