Background-Adiponectin is an adipocyte-derived plasma protein that accumulates in the injured artery and has potential antiatherogenic properties. This study was designed to determine whether a decreased plasma adiponectin level (hypoadiponectinemia) can be independently associated with the prevalence of coronary artery disease (CAD). Methods and Results-The consecutive 225 male patients were enrolled from inpatients who underwent coronary angiography. Voluntary blood donors (nϭ225) matched for age served as controls. Plasma adiponectin levels in the CAD patients were significantly lower than those in the control subjects. Multiple logistic regression analysis including plasma adiponectin level, diabetes mellitus, dyslipidemia, hypertension, smoking habits, and body mass index revealed that hypoadiponectinemia was significantly and independently correlated with CAD (PϽ0.0088). The entire study population was categorized in quartiles based on the distribution of plasma adiponectin levels. The interquartile cutoff points were 4.0, 5.5, and 7.0 g/mL. The multivariate-adjusted odds ratios for CAD in the first, second, and third quartiles were 2.

Background-High-sensitive C-reactive protein (hs-CRP) is a well-known risk factor for coronary artery disease (CAD).Recently, we have demonstrated that adiponectin served as an antiatherogenic plasma protein which was secreted specifically from adipocytes. The present study investigated the association between adiponectin and CRP in the blood stream and adipose tissue. Methods and Results-We studied a total of 101 male patients, 71 of whom had angiographically documented coronary atherosclerosis. As a control group, 30 patients with normal coronary angiogram were included. The plasma hs-CRP levels were negatively correlated with the plasma adiponectin levels (rϭϪ0.29, PϽ0.01). The plasma adiponectin concentrations were significantly lower and the hs-CRP levels were significantly higher in the CAD patients compared with control subjects. The mRNA levels of CRP and adiponectin were analyzed by quantitative real-time polymerase chain reaction method. We found that the CRP mRNA was expressed in human adipose tissue. A significant inverse correlation was observed between the CRP and adiponectin mRNA levels in human adipose tissue (rϭϪ0.89, PϽ0.01).In addition, the CRP mRNA level of white adipose tissue in adiponectin deficient mice was higher than that of wild-type mice. Key Words: coronary disease Ⅲ risk factors Ⅲ inflammation Ⅲ proteins C -reactive protein (CRP) is a well-known systemic marker for inflammation. Previous prospective studies indicate that a chronic low-grade inflammation is involved in the pathogenesis of atherosclerosis, and elevated highsensitive CRP (hs-CRP) level is a risk factor for coronary artery disease (CAD). 1,2 Plasma hs-CRP levels were also strongly associated with obesity and obesity-related diseases, including insulin resistance, diabetes mellitus, and hyperlipidemia. [3][4][5][6] Although a recent report indicated that the plasma hs-CRP level decreased during weight reduction, 6 the precise interaction of CRP with obesity has not been fully elucidated. Conclusions-TheAdipose tissue secretes various bioactive substances, conceptualized as adipocytokines, including leptin, tumor necrosis factor-␣ (TNF-␣), and adiponectin, that may directly contribute to obesity-liked metabolic and vascular diseases. 7,8 Adiponectin is an adipocyte-specific plasma protein that we identified in a human adipose tissue cDNA library. 8 We have reported that physiological concentrations of human recombinant adiponectin suppressed TNF-␣-induced endothelial adhesion molecule expression, macrophage-to-foam cell transformation, and TNF-␣ expression in macrophage and adipose tissue. 9 -12 Recently, we have reported that adiponectin-deficient mice exhibit severe diet-induced insulin resistance and enhanced neointimal thickening after vascular injury. 12,13 Clinically, hypoadiponectinemia was observed in patients with obesity, type 2 diabetes, and CAD. 9,14,15 These findings suggest that adiponectin has antiinflammatory properties and acts as an endogenous modulator of obesity-related diseases. Atherosclerosis can be...

Abstract-Endothelial dysfunction is a crucial feature in the evolution of atherosclerosis. Adiponectin is an adipocytespecific plasma protein with antiatherogenic and antidiabetic properties. In the present study, we investigated the relation between adiponectin and endothelium-dependent vasodilation. We analyzed endothelial function in 202 hypertensive patients, including those who were not taking any medication. Forearm blood flow was measured by strain-gauge plethysmography. Plasma adiponectin level was highly correlated with the vasodilator response to reactive hyperemia in the total (rϭ0.257, PϽ0.001) and no-medication (rϭ0.296, Pϭ0.026) groups but not with nitroglycerin-induced hyperemia, indicating that adiponectin affected endothelium-dependent vasodilation. Multiple regression analysis of data from all hypertensive patients revealed that plasma adiponectin level was independently correlated with the vasodilator response to reactive hyperemia. Vascular reactivity was also analyzed in aortic rings from adiponectinknockout (KO) and wild-type (WT) mice. Adiponectin-KO mice showed obesity, hyperglycemia, and hypertension compared with WT mice after 4 weeks on an atherogenic diet. Endothelium-dependent vasodilation in response to acetylcholine was significantly reduced in adiponectin-KO mice compared with WT mice, although no significant difference was observed in endothelium-independent vasodilation in response to sodium nitroprusside. Our observations suggest that hypoadiponectinemia is associated with impaired endothelium-dependent vasorelaxation and that the measurement of plasma adiponectin level might be helpful as a marker of endothelial dysfunction.

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The I164T mutation in the adiponectin gene was a common genetic background associated with the metabolic syndrome and CAD in the Japanese population.

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Background-Takayasu arteritis (TA) is a chronic vasculitis that primarily affects large elastic arteries. Monitoring of disease activity is crucial because the disease tends to progress despite treatment with glucocorticoid and/or immunosuppressive agents. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have generally been used as disease activity markers, but these are nonspecific inflammatory markers and lack the sensitivity and specificity to accurately monitor the disease status. Given the histological findings characterized by destruction of elastic fibers, we hypothesized that matrix metalloproteinases (MMPs) could be useful as markers of disease activity in TA. Methods and Results-A consecutive series of 25 patients with TA were enrolled in this study. According to the National Institutes of Health criteria of disease activity, 11 were in an active phase and the remaining 14 were in remission. Circulating levels of MMP-2, MMP-3, and MMP-9 were determined by ELISA in all patients with TA and controls. MMP-2 levels were higher in patients with TA than in controls, but no correlation was found between serum MMP-2 and disease activity score. In contrast, MMP-3 and MMP-9 levels in patients with active disease were higher than in patients in remission and controls, and a positive correlation was demonstrated between circulating levels of MMP-3 or MMP-9 and disease activity score. The high levels of MMP-3 and MMP-9 improved when patients underwent remission. Conclusions-The present results indicate that MMP-2 can be helpful in diagnosing TA and that MMP-3 and MMP-9 can be used as activity markers for TA.

The present study was designed to evaluate the metabolism of chylomicron and chylomicron remnants by measuring serum apolipoprotein B-48 (apoB-48) levels in 335 normolipidemic and 253 hyperlipidemic subjects using a novel ELISA system. The distribution of fasting serum apoB-48 levels in normolipidemic subjects varied widely, ranging from Ͻ 1 to Ͼ 24 g/ml (mean, 5.2 ؎ 3.8 g/ml; median, 3.9 g/ml). Serum apoB-48 levels correlated with serum triglyceride (TG) concentrations ( r ‫؍‬ 0.45, P Ͻ 0.001), but not with total cholesterol levels. Serum apoB-48 levels were 7 to 18 times higher in patients with Type I, Type V, and Type III hyperlipidemia, and only slightly higher in patients with Type IIa, Type IIb, and Type IV hyperlipidemia, compared with normolipidemic subjects. The calculated apoB-48/ TG ratio was elevated only in patients with dysbetalipoproteinemia (apoE2/2 phenotype). In normolipidemic subjects, oral fat loading resulted in about 2-fold increase in serum apoB-48 levels, with a peak level recorded at 3-4 h postloading, and then returned to the baseline level within 6 h. On the other hand, in patients with dysbetalipoproteinemia, serum apoB-48 levels did not change considerably. Our results indicate that serum apoB-48 is a very useful parameter for evaluating lipoprotein metabolism in exogenous pathways. The pathogenic role of hypertriglyceridemia in atherosclerosis has long been elusive. A recent meta analysis of several cohort studies revealed that plasma triglyceride (TG) level is an independent risk factor for cardiovascular diseases (1). The relationship between plasma TG levels and atherosclerotic diseases has often been discussed in relation to postprandial hyperlipidemia (2-7). Several studies have pointed to the relationship between the impaired metabolism of postprandial TG-rich lipoproteins (TRLs) and the presence or development of coronary heart disease (CHD). A mechanistic hypothesis linking the postprandial generation of TRL remnants (products of lipolytic degradation of TRL produced by the liver, VLDL, and by the intestine chylomicrons) to the development of atherosclerosis was formulated almost 20 years ago by Zilversmit (8). TG-depleted remnants are considered to be atherogenic because they can penetrate the mucosal lining of the arterial wall and become entrapped within the subendothelial space. Thus, accurate evaluation of the kinetics of chylomicron and chylomicron remnants is very important.Chylomicrons are secreted by the intestine after fat ingestion. Chylomicron particles contain apolipoprotein B-48 (apoB-48) as the structural protein, which in humans is formed exclusively in the intestine after tissue-specific editing of the apoB-100 mRNA (9, 10). Different methods are used for estimation of postprandial lipoproteins. A number of studies have made use of retinyl palmitate (RP) labeling of chylomicrons, together with postprandial plasma TG quantification. The RP technique has shortcomings as it has recently been shown that RP can exchange between lipoprotein species in pla...