The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Correlation of Neopterin and TNF-alpha with Asymmetric Dimethylarginine in Metabolic Syndrome
No full textBACKGROUND: A large number of obesity in the community increases the incidence of Metabolic Syndrome (MetS) that can increase the risks of heart disease, diabetes, and stroke. One of the possible causes of stroke is atherosclerosis. Atherosclerosis is initiated by the incidence of inflammation and endothelial dysfuction. Atherosclerosis is involved in an ongoing inflammatory response. At the beginning of atherosclerosis, when the endothel become inflamed, it expresses adhesion molecules that attract monocytes. The monocytes then migrate into the intima due to endothelial dysfunction. Activation of macrophage occurs in the process of inflammation as the earliest type of lesion of atherosclerosis. In this study, monocyte/macrophage activation is marked by Neopterin. In other process of atherosclerosis, vascular nitric oxide (NO) activity has a role as a potent endogenous vasodilator. In regulating the vascular tone, NO has a role to suppress vascular smooth muscle proliferation, inhibit platelet adhesion and aggregation, and interferes with the leukocyte-endothelial cell interaction. In MetS, hypercholesterolemia decreases NO activity. Asymmetric Dimethylarginine (ADMA) has been characterized as an endogenous, competitive inhibitor of NO synthase. In this study, the incidence of endothelial dysfunction is marked by ADMA. The aim of this study was to discover the role of Neopterin in MetS patients by evaluating the correlation between Neopterin and ADMA in MetS through tumor necrosis factor (TNF)-α or direct line.METHODS: The study was cross sectional on 64 males with MetS aged 30-65 years. The measurements of TNF-α concentrations was done, respectively.RESULTS: Neopterin concentration correlated with Log TNF-α concentration (r=0.311, p=0.012). There is no significant correlation between Neopterin and ADMA (r=0.012, p=0.930); ADMA and Log TNF-α (r=0.029, p=0.821).CONCLUSIONS: There is no significant correlation between Neopterin and ADMA through TNF-α or direct line.KEYWORDS: MetS, Neopterin, ADMA, NO, TNF-
Correlation between hsCRP and Anti-beta2GPI Antibody in Metabolic Syndrome
No full textBACKGROUND: Several researches reported that inflammatory and immunological mechanism such as autoantibody to β2-glycoprotein I (anti β2GPI) appear as related factors in initiation and progress of atherosclerosis lesion in patient with autoimmune disease. Antibody to β2GPI titers are correlated with atherosclerosis and in vitro studies showed that they enhance oxidized low density lipoprotein (ox-LDL) uptake by macrophages. Immunization with auto-antigen β2GPI elicits an immune response to influence lesion progression that mostly happens in autoimmune subjects. The metabolic syndrome (MetS) is combination of several metabolic disorders such as obesity, dyslipidemia, Diabetes Mellitus (DM) and conditions due to inflammation and stress oxidative. The Correlation between inflammatory markers such as High sensitivity C-Reactive Protein (hsCRP) and anti-β2GPI antibody in MetS needs to be further investigated.METHODS: This was an observational study with cross sectional design on subject with MetS as determined by the International Diabetes Federation (IDF) 2005’s criteria.RESULTS:There was a positive and significant correlation between hsCRP and anti-β2GPI antibody in MetS group (r=0.406; p≤0.05) as compared to non-MetS group. We found that there was elevated level of anti-β2GPI antibody in hsCRP of 3-10 mg/L.CONCLUSIONS: Anti-β2GPI antibody may be elevated in subjects with MetS who have low grade of inflammation as shown by hsCRP.KEYWORDS: metabolic syndrome, inflammation, autoantigen, atherosclerosis, obesit
Nephroprotective Effect of Pentoxyphylline Through Improvement in the Expression of TGF-beta1, Collagen Type-1, and Renal Interstitial Fibrosis in Swiss Strain Mice After Being Induced by Doxorubicin
No full textBACKGROUND: Use of doxorubicin (DXR) in the treatment of cancer has been increasing along with the increase in cancer morbidity. Nephrotoxic effects of DXR are still a problem. Pentoxyphylline (PTX) as an electron-donor material can be nephroprotective, so the combination of DXR and PTX might reduce the nephrotoxic effects of DXR. The aim of this study was to prove the nephroprotective effect of PTX and DXR nephrotoxicity through the improvement of TGF-β1, collage type-1, and renal interstitial fibrosis.METHODS: Twenty-four males Swiss strain mice, divided into three groups namely Control (C) injected with NaCl 0.9%; DXR induced nephrotoxicity (D); and effect of PTX on D (P/D) by intraperitoneally, respectively, each group consisted of 8 mice. Injections were given once a week for three consecutive weeks. At 8th week post-treatment, all eight mice of each group were sacrificed. Examination of TGF-β1 and collagen type-I expression was done by immunohistochemistry with monoclonal antibody. Renal interstitial fibrosis examination was done by a histopathologist, using Verheoff van Giesen staining. The statistic analysis was carried out using one-way ANOVA.RESULTS: TGF-β1 expression increased from C to D and subsequently decreased in P/D (4.50±3.89 vs. 177.88±68.78 vs. 36.88±9.51). Collagen type-I expression increased from C to D and subsequently decreased in P/D (12.00±14.32 vs. 186.25±125.62 vs. 36.00±29.14). Renal interstitial fibrosis expression increased from C to D and subsequently decreased in P/D (16.75±6.14 vs. 85.00±7.33 vs. 60.50±11.40). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were higher significantly in D group as compared to C group (p<0,001). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were lower significantly in P/D group as compared to D group (p<0.005).CONCLUSIONS: PTX was proved to be nephroprotector inducing by DXR.KEYWORDS: PTX, nephroprotector, TGF-β1, collagen type-I, renal interstitial fibrosi
The Relationship of Osteoprotegerin, Matrix Gla Protein, and HbA1C in Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients
No full textBACKGROUND: Many studies have reported that diabetes mellitus correlates with vascular calcification event that increases progressively in uncontrolled diabetes. Osteoprotegerin (OPG) is known to act as a promoter in vascular calcification, contrary to Matrix Gla Protein (MGP), which is an inhibitor in vascular calcification. The aim of this study was to observe the progress of vascular calcification in uncontrolled diabetes patients by assessing biochemical markers OPG as promoter and MGP as inhibitor in vascular calcification.METHODS: This was an observational study with cross sectional design on adult male patients with type 2 diabetes mellitus, defined by DM Consensus Criteria Indonesia, 2006.RESULTS: The results of this study showed that there was a positive significant correlation between OPG and HbA1c (r=0.261, p=0.030), in contrast with MGP that showed no significant correlation with HbA1c. OPG also correlated significantly with Fasting Plasma Glucose (r=0.261, p=0.014). In uncontrolled diabetes group there was positive significant correlation between OPG and HbA1c (r=0.397, p=0.014). There was no significant difference found in the levels of OPG in controlled and uncontrolled diabetes groups (p=0.567), but OPG/MGP index showed higher difference (p=0.259). The OPG/MGP index also had positive significant correlation with HbA1c (r=0.285, p=0.018) and Fasting Plasma Glucose (r=0.313, p=0.009).CONCLUSIONS: This study suggested progress to vascular calcification in uncontrolled type 2 diabetes mellitus. The use of vascular calcification biomarkers are recommended to predict/detect vascular calcification event in type 2 diabetes mellitus patients.KEYWORDS: type 2 diabetes mellitus, vascular calcification, OPG, MGP, HbA1
HDL: More Than Just Cholesterol
Get PDFBACKGROUND: Plasma concentration of high density lipoprotein cholesterol (HDL-C) are strongly, consistenly, and independently inversely associated with risk of atheroschlerotic cardiovascular disease (CVD). However, the last decade has seen several observations that do not follow this simple script.CONTENT: A proteomic analysis of HDL has given us an intriguing glimpse into novel components of HDL. HDL isolated from normal humans contains several classes of proteins, including not only apolipoproteins, but also complement regulatory proteins, endopeptidase inhibitors, hemopexin, and acute phase response proteins. These observations raise the possibility of unsuspected roles for HDL. HDL delivery of complement proteins would implicate HDL in innate immunity. Serine proteinase inhibitors would enable HDL to modulate proteolysis of the vessel wall. HDL from patients with coronary artery disease was enriched in apoE, apoC-IV, apoA-IV, Paraoxonase (PON), and complement factor C3. Highlighted additional mechanisms through which HDL protects the vessel wall are: HDL improves vascular function, decreases vascular inflammation, detoxifies radicals, and limits thrombosis.SUMMARY: Both inter- and intra-organ desynchrony may be involved in the pathogenesis of cardiometabolic disease attributable to effects in brain and multiple metabolic tissues including heart, liver, fat, muscle, pancreas, and gut. Efforts to dissect the molecular mediators that coordinate circadian, metabolic, and cardiovascular systems may ultimately lead to both improved therapeutics and preventive interventions.KEYWORDS: HDL, Apo–A1, RCT, inflammation, HDL dysfunction, HDL proteome, HDL & Apo–A1 mimetic
The Correlation between Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and Insulin Resistance and the Components of Atherogenic Lipoprotein Phenotype in Males with Central Obesity
No full textBACKGROUND: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) promotes the degradation of LDL receptor in hepatocytes. in vitro studies have proven that insulin increases the expression of PCSK9. Insulin resistance, a common condition in central obesity is characterized by dyslipidemia called Atherogenic Lipoprotein Phenotype (ALP). This study aimed to investigate the correlation between insulin resistance (HOMA-IR) and PCSK9, and to analyze whether this condition is related to the development of ALP in central obesity.METHODS: This is an observational study with crosssectional design. The subjects consisted of 62 male adults with central obesity, aged 30-60 years old. ELISA was used to measure plasma PSCK9.RESULTS: The mean plasma PCSK9 concentration of the samples was 283.7 ng/mL. PCSK9 had positive linear correlation with HOMA-IR (r=0.225, p=0.045) and Apo B (r=0.245, p=0.055). After controlling of HOMA-IR, PCSK9 had positive linear correlation with triglycerides (r=0.352, p=0.045). In population with HOMA-IR >2, crosstabs analysis showed that PCSK9 had significant correlation with triglycerides and Apo B with an odd ratio of 6,125 (r=0.376, p=0.037). Triglyceride showed significant negative correlation with HDL cholesterol and ratio of LDL/Apo B, but neither HOMA-IR nor PCSK9 did.CONCLUSION: In males with central obesity, PCSK9 is one of the factors mediating the occurence of ALP in insulin resistance.KEYWORDS: PCSK9, insulin resistance, atherogenic lipoprotein phenotyp
Circadian Clock and The Cardiometabolic Risk
No full textBACKGROUND: Epidemiological data reveal parallel trends of decreasing sleep duration and increases in metabolic disorders such as obesity, diabetes and hypertension. There is growing evidence that these trends are mechanistically related.CONTENT: The circadian system orchestrates the temporal organization of many aspects of physiology, including metabolism, in synchrony with the 24 hours rotation of the Earth. The circadian system is a complex feedback network that involves interactions between the central nervous system and peripheral tissues. Circadian regulation is intimately linked to metabolic homeostasis and that dysregulation of circadian rhythms can contribute to disease. Conversely, metabolic signals also feed back into the circadian system, modulating circadian gene expression and behavior.SUMMARY: Both inter- and intraorgan desynchrony may be involved in the pathogenesis of cardiometabolic disease attributable to effects in brain and multiple metabolic tissues including heart, liver, fat, muscle, pancreas and gut. Efforts to dissect the molecular mediators that coordinate circadian, metabolic, and cardiovascular systems may ultimately lead to both improved therapeutics and preventive interventions.KEYWORDS: circadian rhythms, clock genes, nuclear receptor, sleep, obesity, cardiometabolic ris
Correlation between Circulating Levels of Pro-Inflammatory Cytokines TNF-alpha and Vascular Calcification Inhibitor Matrix Gla Protein in Obese Men
No full textBACKGROUND: Adult obesity is rapidly increasing in the world including Indonesia. Tumor necrosis factor α (TNF-α) was chronically elevated in obese adipose tissue. TNF-α, a pleiotropic cytokine and also a regulator of bone formation, may might represent an important link between obesity and vascular calcification. Elegant genetic studies in mice and human have highlighted the important roles for Matrix Gla Protein (MGP) as an inhibitor of vascular calcification. The aim of this study was to examine the correlation between circulating levels of pro-inflammatory cytokines TNF-α and vascular calcification inhibitor MGP in obese men.METHODS: This was an observational cross-sectional study including 40 central obese men (waist circumference ≥90 cm) aged 31-60 years old. Serum MGP and serum TNF-α concentrations were quantified by ELISA principle. Fasting plasma glucose was assessed using hexokinase methods, triglyceride by GPO-PAP methods, and creatinine by Jaffe methods. All assays were performed according to the manufacture instruction. Statistical analysis was performed with SPSS for windows ver 16. Univariate analysis were performed to analyze mean, maximum, minimum value and SD. Pearson correlation statistic were performed to determine the correlation between variables. Significance value were define as alpha level = 0.05 based on two-tailed tests.RESULTS: The cross-sectional study (n=40) showed that the advancing age was correlated with plasma TNF-α concentration (r=0.348; p=0.028). The mean concentration of TNF-α and MGP were 8.323 and 8.368, respectively. We found a significant negative correlation between TNF-α with MGP (r=-0.425; p=0.006) and a significant correlation between TNF-α and triglyceride (r=0.375; p=0.017).CONCLUSIONS: Circulating level of TNF-α was inversely correlated with MGP concentration in obese men. This finding suggested that high level TNF-α leads to low MGP concentration obese men, hence, limits inhibitory capacity in vascular calcification.KEYWORDS: hypertension, obesity, vascular calcification, MGP, TNF-
The Role of Angiopoietin-like Protein 3 and Fibroblast Growth Factor 21 to Lipolysis, Inflammation and Insulin Resistance in Indonesian Non-Diabetic Obese Male
No full textBACKGROUND: Obesity is commonly associated with a systemic low grade inflammation and insulin resistance state. Although it is still being debated, increased lipolysis is known as one of the risk factors for inflammation and insulin resistance. Two factors already known to affect lipolysis are Angptl3, known as prolipolytic factor, and FGF21, known as antilipolytic factor. The aim of this study was to observe the role of Angptl3 and FGF21 to lipolysis, inflammation and insulin resistance in non diabetic obese male.METHODS: This was an observational study with cross sectional design. One hundred and thirty male subjects aged 30-60 years with non diabetic abdominal obesity characterized by waist circumference 97.32±5.63 cm and fasting blood glucose 90.19±8.78 mg/dL.RESULTS: The results of this study showed a correlation between Angptl3-FFA (r=0.203; p=0.021; R square=0.041; p=0.021), Angptl3-FABP4 (r=0.330; p=0.000; R square=0.109; p=0.000) and Angptl3-TNFα (r=0.288; p=0.001; R square=0.049; p=0.011). There was a correlation between FGF21-FABP4 (r=0.218, p=0.013; R square=0.047, p=0.013) and FGF21 HOMA-IR (r=0.308, p=0.000; R square=0.046, p=0.014).CONCLUSIONS: We conclude that Angptl3 may affect lipolysis and inflammation while FGF21 may affect lipolysis and insulin resistance. The increased FGF21 concentration might occur as a compensation (negative feedback mechanism) to reduce lipolysis and increase insulin sensitivity in non diabetic obese males. Further studies might be needed to observe Angptl3 and FGF21 profile in more severe obese population in Indonesia.KEYWORDS: obesity, lipolysis, inflammation, insulin resistanc
Correlation Between Adiponectin, Tumor Necrosis Factor-alpha, Insulin Resistance and Atherogenic Dyslipidemia in Non Diabetic Central Obese Males
No full textBACKGROUND: Obesity raises the risk for atherosclerotic cardiovascular disease (ASCVD) through many risk factors including atherogenic dyslipidemia. Atherogenic dyslipidemia is characterized by high levels of triglyceride, increased small dense low density lipoprotein particles, and reduced levels of high density lipoprotein cholesterol. The exact mechanisms of central obesity and this atherogenic lipoprotein phenotype (ALP) is not clearly understood. Central obesity is characterized by a state of systemic low grade inflammation and insulin resistance. Adipose tissue has recently been shown to secrete a variety of bioactive peptides, called adipocytokines, that can potentially affect glucose and lipid metabolism. The aim of this study was to observe the role of adiponectin, tumor necrosis factor-α (TNF- α) and insulin resistance in atherogenic dyslipidemia in nondiabetic central obese males.METHODS: This was a cross-sectional study on 75 non-diabetic central obese male subjects (waist circumferences > 90 cm). Adiponectin and TNF-α testing were performed by ELISA; insulin resistance was assessed by the Homeostasis Model Assessment (HOMA) index, triglyceride was assessed by GPO-PAP, HDL cholesterol and small dense LDL were measured by homogenous method. Statistical analysis was done by SPSS for Windows v. 11.5 with a significance level at p < 0.05. The Pearson and Spearman’s Rho correlation coefficient was used to assess the correlation between various anthropometric and biochemical parameters.RESULTS: There were 75 patients aged 38.0±6.3 years, Adiponectin concentration was 3.55±1.38 μg/ml, HOMA index was 2.28±1.63, TNF-α was 12.42±11.25 pg/ml, triglyceride was 185.17±109.00, HDL-cholesterol was 44.15±9.23 mg/dL, small dense LDL 23.22±12.26 mg/dL. This study revealed that there were correlations between adiponectin and triglyceride (r=-0.236, p=0.042), adiponectin and HDL cholesterol (r=0.300, p=0.009), adiponectin and atherogenic dyslipidemia (r=-0.256, p=0.027), whereas there was no correlation between insulin resistance and TNF-α with the atherogenic dyslipidemia.CONCLUSION: Adiponectin might contribute to atherogenic dyslipidemia in central obese non-diabetic males. Advancing our understanding of the function and measurement of adiponectin serum concentration will be useful in clinical diagnosis of obesity related atherogenic dyslipidemia.KEYWORDS: obesity, waist circumference, adiponectin, insulin resistance, TNF-α, atherogenic dyslipidemi