[Show abstract][Hide abstract] ABSTRACT: Increased visfatin expression has been shown to increase gene expression, which promotes cell survival and increases SirT1 activity thereby promoting angiogenesis. Previous studies have shown that oral squamous cell carcinomas (OSCCs) express high levels of activated signal transducer and activator of transcription 3 (Stat3). Since visfatin expression is increased by Stat3, we hypothesized that visfatin protein may be highly expressed in OSCCs. Immunohistochemistry was the technique used to examine the expression of visfatin in 19 OSCCs and 4 hyperplastic lesions. The results indicated that visfatin was detected in the cytoplasm and nuclei of the OSCCs and epithelial hyperplasia as well as in the stromal tissues of patients with OSCC and oral hyperplasia. Furthermore, co-expression of visfatin and proliferating cell nuclear antigen proteins was noted in verrucous epithelial hyperplasia, and co-expression of visfatin and CD68 in the inflammatory cells of the stromal region was noted in the OSCCs. In addition, enzyme-linked immunosorbent assay showed that plasma visfatin concentrations were significantly increased in the patients with OSCC and oral hyperplasia compared to those of the control subjects. In conclusion, visfatin expression and concentrations were higher in OSCCs and oral hyperplasia, suggesting that visfatin may play a role in the pathogenesis of oral cancers.
Journal of applied biomedicine 08/2014; · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: p-Cresylsulphate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. Furthermore, previous studies were also found the association among serum total PCS, major adverse cardiovascular events, and all-cause mortality. However, little is known about the relationship between total PCS level and prolonged QT interval. We assessed whether serum total PCS level is related with prolonged QT interval by measuring 12-lead electrocardiogram (ECG) recording in stable angina patients with early stage of renal failure.
[Show abstract][Hide abstract] ABSTRACT: Introduction. Visfatin (also known as pre-B cell colony-enhancing factor) is increased in patients with chronic kidney disease and has been linked with coronary atherosclerosis. Given that it has been reported that visfatin plays a role in endothelial dysfunction in chronic kidney disease patients, we examined associations between visfatin levels and several markers related to atherosclerosis. Materials and Methods. The association between visfatin and atherosclerotic risk factors was studied in 173 chronic kidney disease patients (130 men and 43 women). Serum levels of visfatin were measured by the enzyme-linked immunosorbent assay. Results. With increasing visfatin tertiles, patients proved to have a larger number of vessels with stenosis and a higher likelihood of coronary artery disease, as well as having incrementally lower estimated glomerular filtration rate and serum albumin and higher total leukocyte, neutrophil, and monocyte counts; high-sensitivity C-reactive protein; and brain natriuretic peptide levels. Visfatin showed significant positive correlations with low-density lipoprotein cholesterol, uric acid, blood urea nitrogen, creatinine, brain natriuretic peptide, E-selectin, total leukocyte count, neutrophil count, and high-sensitivity C-reactive protein, and a significant negative correlation with estimated glomerular filtration rate and albumin. Only E-selectin was independently associated with visfatin in multiple linear regression analysis. Conclusions. This study indicates that plasma visfatin levels are significantly higher in the presence of coronary artery disease and are correlated with E-selectin levels, which suggest that increased plasma visfatin may be involved in the pathogenesis of coronary atherosclerosis in CKD patients.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Secreted frizzled-related protein 5 (Sfrp5), an endogenous inhibitor of wingless-type MMTV integration site family (Wnt) signaling, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes mellitus (T2DM). Wnt member 5a (Wnt5a) is a representative ligand and recent reports suggest that Wnt5a is involved in inflammatory diseases and metabolic disorders. The aim of this study was to investigate whether plasma Wnt5a and Sfrp5 levels are altered in patients with T2DM. METHODS: Plasma Sfrp5 as well as Wnt5a concentrations were measured through ELISA in type 2 diabetic and nondiabetic subjects. RESULTS: A total of 82 patients with T2DM and 42 non-diabetic subjects were studied. Plasma Sfrp5 levels were found to be elevated in patients with T2DM (9.4 ± 9.0 vs. 7.4 ± 10.9 ng/mL, P = 0.006). In contrast, Wnt5a levels were decreased (6.8 ± 12.6 vs. 9.1 ± 4.0 ng/dL, P < 0.001). Increasing concentrations of Sfrp5 were independently and significantly associated with T2DM. Multiple logistic regression analysis revealed Sfrp5 as an independent association factor for T2DM, even after full adjustment of known biomarkers. In a multiple linear regression analysis, only the fasting glucose level was positively associated with the plasma Sfrp5 level. CONCLUSIONS: Our results indicate that Sfrp5 may play a role in the pathogenesis of T2DM. This article is protected by copyright. All rights reserved.
Diabetes/Metabolism Research and Reviews 05/2013; · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Indoxyl sulfate (IS) is linked to endothelial damage, NF-κB activation and induced development of atherosclerosis. The purpose of this study was to investigate the relationship between serum IS levels and the severity of coronary artery stenosis. In addition, the relationship among IS and various cardiovascular risk factors was also explored. Methods: Serum IS concentrations were measured using ultra performance liquid chromatography in 191 consecutive patients presenting with stable angina. The associations between serum IS levels and angiographic indexes of the number of diseased vessels, modified Gensini scores and calcium scores were determined. Results: Patients with significant coronary artery stenosis were found to have higher serum IS levels than patients with normal coronary arteries. Using multivariate analysis, serum IS levels were found to be independently associated with the presence and severity of coronary artery disease (CAD). Furthermore, statistically significant correlation was observed between the serum IS levels and age, Agatston calcium score, volume calcium score, modified Gensini score, coronary lesions, coronary disease and Framingham-10 year risk score. Conclusion:This study indicates that serum IS levels are significantly higher in the presence of CAD and correlate with the severity of the disease and coronary atherosclerosis scores, which suggest that increased serum IS may be involved in the pathogenesis of coronary atherosclerosis.
Clinical and investigative medicine. Medecine clinique et experimentale 01/2013; 36(1):E42. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Cardiovascular disease is prevalent among patients with chronic kidney disease (CKD). Patients with CKD have elevated levels of p-cresylsulfate (PCS), which has been linked with cardiovascular mortality in this population. The aim of this study was to evaluate the clinical significance of CKD in coronary artery disease (CAD) patients and to investigate whether a significant correlation exists between CKD, total PCS and poor clinical outcomes in CAD patients. Methods: We assessed the occurrence of major adverse cardiac events (MACEs) among 340 consecutive CAD patients who enrolled in a disease management program after the patients were discharged from the hospital. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m2. Results: Kaplan-Meier analysis revealed that CKD and high total PCS levels (>1.66 mg/L) were significantly associated with the occurrence of MACE. A multivariate Cox hazard regression model revealed that the predictive independent risk factor for the occurrence of MACE was high total PCS level (relative risk = 1.387). We divided the patients with or without CKD and high or low total PCS levels into 4 groups according to their eGFR and total PCS levels, respectively. The hazard ratio for MACE in the group with both CKD and high total PCS level was 1.721, relative to the group without CKD that had low total PCS level (p=0.005). Conclusions: A high serum level of total PCS may be a predictor of elevated risk of MACE in CAD patients with low eGFR.
Journal of nephrology 03/2012; · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We demonstrated that visfatin expressed in monocytes and neutrophils and increased their reactivity in male acute ST-segment elevation myocardial infarction patients. Furthermore, visfatin was strongly appeared in lipid rich coronary rupture plaques and macrophages. These results suggest another explanation about leukocytes mediated visfatin that may play a pathogenesis role in coronary vulnerable plaques rupture.
Mediators of Inflammation 01/2012; 2012:469852. · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Visfatin is a cytokine that is expressed in many tissues, including the heart, and has been proposed to play a role in plaque destabilization leading to acute myocardial injury. The present study evaluates plasma levels of visfatin in acute ST-elevation myocardial infarction (STEMI) patients and examines the temporal changes in visfatin levels from the acute period to the subacute period to determine a correlation with the degree of myocardial ischemia. We evaluated 54 patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP were detected by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model of myocardial infarction (MI). Plasma levels of visfatin were significantly increased in patients with STEMI on admission, relative to controls (effort angina patients and individuals without coronary artery disease). The visfatin levels reached a peak 24h after percutaneous coronary intervention (PCI) and then decreased toward the control range during the first week after PCI. The basal plasma visfatin levels were found to correlate with peak troponin-I, peak creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses confirmed that visfatin levels correlated with the number of diseased coronary arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be higher than in sham-treated mice. IHC analysis showed that visfatin and BNP immunoreactivity was diffusely observable in left ventricular myocytes of the MI mice. This study indicates that plasma visfatin levels are significantly higher in STEMI patients and that these higher visfatin levels correlate with elevated levels of cardiac enzymes, suggesting that increased plasma visfatin may be closely related to the degree of myocardial damage.
[Show abstract][Hide abstract] ABSTRACT: p-Cresylsulphate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. We aimed to investigate the relationship of total PCS with traditional biomarkers associated with chronic coronary atherosclerosis. In addition, the relationship between serum total PCS levels and the severity of coronary artery stenosis was also explored.
Serum total PCS concentrations were measured by using the Ultra Performance LC System in 202 consecutive stable angina patients, and their associations with angiographic indexes of the number of diseased vessels and modified Gensini score were estimated. Patients with significant coronary artery stenosis have higher median serum total PCS levels than patients with normal coronary arteries. Statistically significant associations were observed between the serum total PCS levels and the number of diseased vessels (beta=0.261, p=0.0002), and modified Gensini score (beta=0.171, p=0.016). Using multivariate analysis, serum total PCS level was independently associated with the presence and severity of CAD.
This study indicates that serum total PCS levels are significantly higher in the presence of CAD and are correlated with the severity of the disease, which suggest that increased serum total PCS may be involved in the pathogenesis of coronary atherosclerosis.
[Show abstract][Hide abstract] ABSTRACT: Elevated levels of circulating adiponectin (ADPN), an anti- inflammatory and anti-oxidative peptide, are associated with unfavorable cardiovascular outcomes in patients with cardiovascular diseases. The aim of this study was to investigate whether plasma ADPN levels could help predict major adverse cardiovascular events (MACE) in patients with documented coronary artery disease (CAD). We prospectively enrolled 193 CAD patients, who underwent percutaneous coronary intervention (PCI), and/or stenting and coronary artery bypass graft (CABG) surgery. ELISA was used to measure plasma ADPN concentrations. MACE--myocardial infarction, PCI, CABG, stroke, carotid revascularization, and death--was evaluated during a follow-up period of median 15.3 months (range 5-21 months). Cox regression analysis revealed that diabetes status, waist circumference, and plasma ADPN levels were significantly associated with MACE occurrence. On stratification according to diabetes status, plasma ADPN levels helped predict MACE only in patients with type 2 diabetes mellitus (T2DM). Kaplan-Meier analysis revealed higher MACE rates in diabetic patients with high-plasma ADPN levels than in those with low-plasma ADPN levels. High ADPN plasma concentrations can independently be associated with MACE in CAD with T2DM but not in those without diabetes. This indicates that plasma ADPN may have potential roles in high risk T2DM patients with ischemic heart disease.
[Show abstract][Hide abstract] ABSTRACT: Indoxyl sulphate (IS) and p-cresylsulphate (PCS) are uremic toxins with similar protein-binding, dialytic clearance, and proinflammatory features. Few studies have evaluated the possible associations between these solutes and coronary artery disease (CAD) in type 2 diabetes (T2D) patients.
A hospital-based case control study was performed. A total of 209 T2D patients were divided into two groups based on the presence/absence of significant CAD (≥50% luminal reduction). Serum total PCS and IS levels were measured using the Ultra Performance LC System. The relationship between total PCS and IS levels were investigated. Coronary calcium scores and the modified Gensini score were analyzed.
Serum total PCS and IS levels were significantly higher in patients with both T2D and significant CAD, than in non-diabetic control subjects and T2D patients without CAD (all p < 0.05). Logistic regression analysis revealed independent and significant associations between the two solutes and CAD status. Serum total PCS, IS, and numbers of diseased vessels were elevated in groups with estimated glomerular filtration rate (eGFR) of 60-89 ml/min/1.73 m2 and below. Also, serum total PCS and IS levels were significantly associated with eGFR, coronary calcium scores, Gensini score, adipocytokines (adiponectin, visfatin, and leptin), and total white blood cell count.
Serum total PCS and IS levels were elevated in patients with T2D and CAD. These increases were associated with renal function deterioration, inflammation, and coronary atherosclerosis.
The Review of Diabetic Studies 01/2010; 7(4):275-84.
[Show abstract][Hide abstract] ABSTRACT: Visfatin/pre-B-cell colony-enhancing factor is a cytokine that is expressed as a protein in several tissues (e.g., liver, skeletal muscle, immune cells), including adipose tissue, and is reported to stimulate inflammatory cytokine expressions and promote vascular smooth cell maturation. Visfatin may act as a proinflammatory cytokine and be involved in the process of atherosclerosis. In this study, we investigated whether plasma visfatin levels were altered in patients with ischemic stroke.
Plasma visfatin concentrations were measured through enzyme immunoassays in patients with ischemic stroke and in control subjects without stroke.
The mean plasma concentration of visfatin in the 120 patients with ischemic stroke was significantly higher than that of the 120 control subjects without stroke (51.5 +/- 48.4 v 23.0 +/- 23.9 ng/mL, P < .001). Multiple logistic regression analysis confirmed plasma visfatin to be an independent factor associated with ischemic stroke. Increasing concentrations of visfatin were independently and significantly associated with a higher risk of ischemic stroke when concentrations were analyzed as both a quartile and a continuous variable. The multiple logistic regression analysis-adjusted odds ratios and 95% confidence intervals for ischemic stroke in the second, third, and fourth quartiles were 2.3 (0.7-7.7), 6.9 (2.2-23.3), and 20.1 (4.9-97.7), respectively. Plasma visfatin concentration was positively associated with high-sensitivity C-reactive protein levels and negatively associated with low-density lipoprotein cholesterol.
Our results indicate that higher visfatin levels are associated with ischemic stroke in the Chinese population.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 09/2009; 18(5):354-9. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While increased arterial stiffness is a known risk of cardiovascular disease, pulse wave velocity (PWV) is a conventionally adopted index of arterial stiffness. However, the relationship between PWV and left ventricular functions are not thoroughly evaluated. This cross-sectional study investigated whether PWV measurement is an early indicator of left ventricular (LV) dysfunction. A noninvasive, volume-plethysmographic apparatus was used to determine blood pressure, electrocardiogram, heart sounds, and PWV in 42 consecutively diagnosed subjects with hypertension, and 42 sex- and age-matched nonhypertension subjects were studied. Arterial stiffness and aortic stiffness were evaluated by brachial-ankle (b-a) PWV, heart-carotid (h-c) PWV, heart-femoral (h-f) PWV, carotid-femoral (c-f) PWV, and femoral-ankle (f-a) PWV. Function of LV was estimated by tissue Doppler imaging (TDI) echocardiography. Hypertension subjects exhibited higher b-a PWV and late diastolic mitral flow velocity values than those of nonhypertensive subjects. Pearson correlation analysis revealed that LV diastolic function (Em(av)) negatively correlated with c-f PWV and b-a PWV. Multiple linear regression analysis indicated that b-a PWV was independently and negatively associated with LV diastolic function (Em(av)). Further analysis by stratified hypertensive status, the b-a PWV were independently and negatively associated with Em(av) in hypertensive subjects (p = 0.004) only. In conclusion, the b-a PWV, but not c-f PWV, h-c PWV, h-f PWV, or f-a PWV, is significantly correlated with LV diastolic function in hypertensive subjects, indicating that b-a PWV involving both central and peripheral components of arterial stiffness may be an early indicator of LV dysfunction.
Clinical and Experimental Hypertension 03/2009; 31(1):31-43. · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epicardial adipose tissue (EAT) is a part of visceral fat deposited around the heart between the pericardium and myocardium along the distribution of coronary arteries. EAT thickness is reported to be associated with coronary atherosclerosis; however, no study has measured EAT volume in patients with type 2 diabetes or investigate its association with coronary artery disease.
A hospital-based case control study.
A total of 49 patients with type 2 diabetes mellitus (T2DM) and 78 nondiabetic controls were studied.
Cardiac multislice computed tomography was used to measure EAT volume, Gensini score, coronary artery calcium score and, coronary lesions. The relationships between EAT volume, markers of coronary atherosclerosis and anthropometric and biochemical parameters of metabolic syndrome (MetS) were investigated.
EAT volume was significantly higher in patients with T2DM than in nondiabetic subjects (166.1 +/- 60.6 cm(3) vs. 123.4 +/- 41.8 cm(3), P < 0.0001). Logistic regression analysis revealed independent and significant associations between EAT and diabetic status. EAT volume was significantly associated with components of MetS (BMI, waist circumference, fasting serum glucose, total cholesterol, HDL-cholesterol, and triglycerides levels), Gensini score, coronary lesions, coronary disease and coronary calcium scores. Univariate, multivariate and trend analyses confirmed that EAT volume was associated with MetS component clustering and the coronary atherosclerosis index.
The analytical results indicate that EAT volume is increased in T2DM patients and is associated with unfavourable components of MetS and coronary atherosclerosis. The close anatomical relationship between EAT and the coronary arteries, combined with other evidence indicating that EAT is a biologically active adipokine-secreting tissue, suggest that EAT participates in the pathogenesis of diabetic coronary atherosclerosis.
[Show abstract][Hide abstract] ABSTRACT: Objectives: Fat surrounding coronary arteries can aggravate coronary artery disease (CAD). To provide evidence for this concept, we sought to investigate the correlation between epicardial adipose tissue (EAT) volumes and risk factors, plasma visfatin levels, inflammatory biomarkers, and the quantity of coronary calcification and atherosclerosis. Methods: EAT volume was measured using cardiac multi-slice computed tomography. Coronary artery calcium (CAC) was determined by the Agatston Score, and plasma visfatin levels were measured by a competitive enzyme immunoassay. Results: Patients with CAC and coronary atherosclerosis had significantly larger EAT volumes than patients without CAC and coronary atherosclerosis. When the analysis was stratified according to diabetes status, the EAT volumes in CAC and coronary atherosclerosis patients, with or without type 2 diabetes, were significantly higher than those of their counterparts. Furthermore, the correlation of EAT volume and CAC remained statistically significant even after it was adjusted for body mass index (BMI). EAT volume was also associated with the Agatston calcium score, volume calcium score, Gensini score, and the Framingham Risk Score. An EAT volume > 200 cm 3 was the strongest independent risk factor for CAC. An elevated EAT volume was also significantly correlated with elevated visfatin, triglycerides, high sensitivity C-reactive protein levels, total white blood cells, lymphocyte counts, and low high-density lipoprotein levels. Conclusion: Increased EAT volumes were associated with coronary atherosclerosis and CAC, independent of risk factors, and were correlated with several CAD inflammatory biomarkers. These data suggest that EAT may act through inflammatory reactions to play an important role in the pathogenesis of coronary atherosclerosis and CAC.