Anti-Apo B-100 Autoantibody is a Marker of Unstable Coronary Plaque.

AIMS: Cardiovascular diseases (CVD) are a global leading cause of mortality. However, few biomarkers are available to predict future coronary plaque rupture. We have recently demonstrated that low levels of anti-apolipoprotein B-100 autoantibody (anti-apo B-100 Ab) correlated with an increased CVD risk in Japanese patients with diabetes. In the present study, we examined the relationship between serum anti-apo B-100 Ab levels and coronary plaque characteristics in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We conducted iMAP®-intravascular ultrasound (IVUS) in 88 Japanese male patients undergoing elective PCI, and the five consecutive slices of IVUS images at the center of the most stenotic culprit lesion were used for identifying the plaque characteristics. The serum levels of anti-apo B-100 Ab against synthetic peptides (p45 or p210) were measured using a homemade enzyme-linked immunosorbent assay. RESULTS: Serum IgG levels of anti-apo B-100 Ab against both native p45 and p210 (IgG N-p45 and IgGN-p210) and malondialdehyde (MDA)-modified p45 and p210 (IgGMDA-p45 or IgGMDA-p210) showed a negative correlation with plaque burden in total male patients undergoing elective PCI. Additionally, both IgGN-p45 and IgGN-p210, but neither IgGMDA-p45 nor IgGMDA-p210, correlated negatively with necrotic and positively with fibrotic components of iMAP®-IVUS plaque characteristics in the patients with ＜1 month statin treatment before elective PCI ("statin-untreated" group). There was no significant correlation between anti-apo B-100 Ab and any plaque characteristics in the patients with statin treatment for 1 month or more before elective PCI ("statin-treated" group). CONCLUSION: Measuring serum levels of anti-apo B-100 Ab might be helpful in the evaluation of unstable coronary plaque in male CVD patients without statin treatment.

Serum Anti-Apo B Antibody Level as Residual CVD Marker in DM Patients under Statin Treatment.

AIM: In the pathogenesis of atherosclerosis, autoantibodies have two-facedness of progression and protection. Previous reports have indicated that low autoantibody levels against apolipoprotein B-100 (apo B-100) could increase the risk of atherosclerotic cardiovascular diseases (CVD) in healthy subjects. In this study, we investigated the relationship between circulating anti-apo B-100 autoantibodies and the clinical parameters in Japanese diabetic patients with or without CVD. METHODS: We measured the serum levels of anti-apo B-100 autoantibodies against native and malondialdehyde (MDA)-modified p45 or p210 epitopes, as well as anti-apo E autoantibodies, using enzyme-linked immunosorbent assay. RESULTS: In patients with CVD, the circulating levels of IgG against native p45, MDA-modified p45, and MDA-modified p210 (IgGN-45, IgGMDA-45, and IgGMDA-210) were significantly lower than those in patients without CVD, whereas no difference was observed in anti-apo E autoantibody levels. In addition, IgMN-45, IgMMDA-45, and IgGMDA-45 were negatively correlated with LDL-C levels, whereas IgGN-45 and IgGN-210 were positively correlated with HbA1c levels. No correlation was observed between autoantibody levels and diabetic microangiopathy. In the statin-treated subgroup, IgGMDA-45 and IgGMDA-210 were significantly lower in patients with CVD than in those without CVD. CONCLUSION: Measurement of serum anti-apo B-100 autoantibodies can be useful for the evaluation of CVD risk in patients with diabetes receiving statin treatment.

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.