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Objective: Atherosclerosis is a disease of blood vessels. Adiponectin is a biomarker of atherosclerosis. Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We investigated the relationship between various serum adiponectin parameters and polyvascular atherosclerosis score assessed by vascular ultrasonography, in subjects with type 2 diabetes mellitus (T2DM)., Methods: The study subjects were 108 outpatients with T2DM who underwent evaluation for atherosclerosis by vascular ultrasonography. Polyvascular atherosclerosis score represented the sum of atherosclerotic abnormalities in the aorta, carotid, renal and common iliac arteries. Blood C1q, total-adiponectin (Total-APN), high molecular weight-adiponectin (HMW-APN) and C1q-APN were measured by enzyme-linked immunosorbent assays. The estimated visceral fat area (eVFA) was measured by bioelectrical impedance., Results: Polyvascular atherosclerosis score correlated only with the C1q-APN/Total-APN ratio (p=0.018 for trend). There were no significant relationships between various adiponectin parameters and carotid maximum intima-media thickness and ankle-brachial index. Age-, sex-, eVFA-adjusted multiple logistic regression analysis that included the above variables identified serum C1q-APN/Total-APN ratio as the only significant and independent determinant of polyvascular atherosclerosis score., Conclusions: Serum C1q-APN/Total-APN ratio correlates with atherosclerosis detected by polyvascular vascular ultrasonography, independent of gender and visceral adiposity, in T2DM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: S100A8/A9 complex is an inflammation-associated biomarker, which binds toll-like receptor 4 and was associated with the receptor for advanced glycation end-products. S100A8 and S100A9 were accumulated in atherosclerotic lesions. High serum levels of S100A8/A9 are associated with acute coronary syndrome and atherosclerosis in type 2 diabetes mellitus (T2DM). However, association between serum S100A8/A9 levels and vulnerable plaque remains unclear. The present study investigated the relation between serum S100A8/A9 levels and relative plaque density (RPD) of the carotid artery determined by ultrasonography in T2DM., Methods: The study subjects were 72 consecutive T2DM outpatients (males/females=42/30), who underwent the carotid artery ultrasonography. RPD in the carotid artery was calculated by the formula; RPD=[density of the carotid plaque/density of vessel lumen]. Serum levels of adiponectin and S100A8/A9 were measured., Results: The median RPD was 2.1. Patients with low RPD (≤2.1) were significantly more likely to have metabolic syndrome, nephropathy, coronary artery disease, and peripheral artery disease, and higher levels of S100A8/A9, S100A8/A9-to-adiponectin ratio, and uric acid, compared to those with high RPD (>2.1)., Conclusions: T2DM patients with low RPD had higher prevalence of metabolic syndrome, cardiovascular diseases and higher serum S100A8/A9 levels, compared to those with high RPD., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Atherosclerosis is a systemic disease of blood vessels. We investigated clinical characteristics of Japanese type 2 diabetic patients with polyvascular lesions detected by systemic vascular ultrasonography. The results showed that the metabolic syndrome correlated with polyvascular lesions detected by systemic vascular ultrasonography in Japanese type 2 diabetics., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Abstract: Objective: Adipose tissue inflammation plays an important role in the pathogenesis of obesity-associated complications, such as atherosclerosis. Adiponectin secreted from adipocytes has various beneficial effects including anti-inflammatory effect. Obesity often presents with hypoadiponectinemia. However, the mechanism and adiponectin movement in obesity remain uncharacterized. Here we investigated tissue distribution of adiponectin protein in lean and obese mice. Methods: Adiponectin protein levels were evaluated by enzyme-linked immunosorbent assay and western blotting. Adipose tissues were fractionated into mature adipocyte fraction (MAF) and stromal vascular fraction (SVF). Results: Adiponectin protein was detected not only in MAF but also in SVF, which lacks adiponectin mRNA expression, of adipose tissue remarkably. SVF adiponectin protein level was higher in obese mice than in lean mice. The mechanism of adiponectin accumulation was investigated in adiponectin-deficient (APN-KO) mice after injection of plasma from wild-type mice. These mice showed accumulation of exogenous adiponectin, which derived from wild type mice, in adipose tissues, and the adiponectin was more observed in SVF of diet induced obese APN-KO mice than lean APN-KO mice. Among the adiponectin binding proteins, T-cadherin mRNA and protein levels in SVF of obese mice were remarkably higher than in lean mice. Oxidative stress levels were also significantly higher in SVF of obese mice than lean mice. Mechanistically, H2O2 up-regulated T-cadherin mRNA level in murine macrophages. Conclusions: The results demonstrated adiponectin targets to adipose SVF of obese mice. These findings should shed a new light on the pathology of adipose tissue inflammation and hypoadiponectinemia of obesity. [Copyright &y& Elsevier]

Adiponectin is exclusively synthesized by adipocytes and exhibits anti‐diabetic, anti‐atherosclerotic and anti‐inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin‐deficient (KO) mice. WT mice were parabiosed with WT mice (WT–WT) or KO mice (WT–KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT–KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT–KO mice. In the diet‐induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet‐induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity. [ABSTRACT FROM AUTHOR]

Aims: Inflammation is closely associated with the development of atherosclerosis and metabolic syndrome. Adiponectin, an adipose-derived secretory protein, possesses an anti-atherosclerotic property. The present study was undertaken to elucidate the presence and significance of adiponectin in vasculature. Methods and Results: Immunofluorescence staining was performed in aorta of wild-type (WT) mice and demonstrated that adiponectin was co-stained with CD31. Thoracic aorta was cut through and then aortic intima was carefully shaved from aorta. Western blotting showed the existence of adiponectin protein in aortic intima, while there was no adiponectin mRNA expression. Adiponectin knockout (Adipo-KO) and WT mice were administered with a low-dose and short-term lipopolysaccharide (LPS) (1 mg/kg of LPS for 4 hours). The endothelium vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were highly increased in Adipo-KO mice compared to WT mice after LPS administration. Conclusions: Adiponectin protein exists in aortic endothelium under steady state and may protect vasculature from the initiation of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is an age-related disease. Adiponectin and C1q form a protein complex in human blood, and that serum C1q and C1q-binding adiponectin (C1q-APN) concentrations can be measured. We investigated circulating C1q and C1q-APN levels in Japanese men including elderly men. Findings: The study subjects were 509 Japanese men including elderly men. Serum levels of total adiponectin (Total-APN), high-molecular weight-adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assay. Total-APN, HMW-APN and C1q-APN, but not C1q, correlated significantly and positively with aging (r=0.26, r=0.24, r=0.17, p<0.01, respectively). The HMW-APN/Total-APN ratio correlated significantly and positively with aging (r=0.14, p<0.01). The C1q-APN/Total-APN ratio and C1q-APN/HMW-APN ratio correlated significantly and negatively with aging (r=-0.17, p<0.01, r=-0.12, p=0.01). C1q-APN/C1q correlated significantly and positively with aging (r=0.09, p=0.03). Multiple regression analysis identified age and body mass index as significant determinants of C1q-APN. Conclusions: The present study demonstrates that serum HMW-APN, C1q-APN, and Total-APN, but not C1q, correlated positively with aging. These preliminary results could form the basis for future research. Trial registration: Clinical Trial Registration Number: UMIN000004318 [ABSTRACT FROM AUTHOR]

Background: Patients on maintenance hemodialysis (HD) have much higher levels of adiponectin (Total-APN). Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We recently reported that C1q-APN/Total-APN ratio rather than Total-APN correlated with atherosclerosis in diabetics. However, the characteristics of C1q-APN in HD patients remain unclear. The preset study investigated the characteristics of the adiponectin parameters including C1q-APN and also to clarify the relationship between various serum adiponectin parameters and atherosclerotic cardiovascular diseases (ACVD) in HD patients. Methods: The single cross-sectional study subjects were 117 Japanese patients (males/females = 61/56) on regular HD. Blood Total-APN, high molecular weight-adiponectin (HMW-APN), C1q-APN and C1q concentrations were measured by enzyme-linked immunosorbent assays. ACVD were defined as stroke, coronary and peripheral artery diseases, thoracic and abdominal aneurysms. Results: Stepwise regression analysis identified high-density lipoprotein-cholesterol (HDL-C) as the only significant and independent determinant of C1q-APN in males, and duration of HD as the only significant and independent determinant of C1q-APN in females. Stepwise regression analysis identified uric acid, low-density lipoproteincholesterol and triglyceride as significant and independent determinants of C1q-APN/Total-APN ratio in males, and leukocyte count and HDL-C as significant and independent determinants of C1q-APN/Total-APN ratio in females. Multiple logistic regression analysis identified inorganic phosphorus and C1q-APN or C1q-APN/C1q ratio as significant determinants of ACVD. Conclusions: Low serum C1q-APN and C1q-APN/C1q ratio, but not C1q-APN/Total-APN ratio, correlated with ACVD in HD patients. [ABSTRACT FROM AUTHOR]

Abstract: S100A8/A9 complex, calprotectin, which serves as an endogenous ligand for immune pathways, is associated with atherosclerosis. These proteins are reported to have several functions such as activating NADPH oxidase, binding toll-like receptor 4 and associated with the receptor for advanced glycation end-products. We recently reported S100A8 mRNA was highly expressed in mouse white adipose tissues and differentiated 3T3-L1 adipocytes. However, regulation of S100A9 expression in murine adipose tissue remains to be elucidated. The results of our studies in male Japanese, obese and control mice and cultured cells showed: (1) serum levels of S100A8/A9 complex, calprotectin, correlated with visceral fat area, body mass index, subcutaneous fat area, and leukocyte count in 500 Japanese men, and (2) higher mRNA expression levels of S100A8 in mature adipocyte fraction and S100A9 in stromal vascular cell fraction of obese mice, compared with those of lean mice. Overexpression of S100A8 and S100A9 in obese adipose tissue may be involved, at least partly, in not only high circulating levels of S100A8/A9 complex in abdominal obesity but also adipose and systemic tissue inflammation. [Copyright &y& Elsevier]