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Correlation between F2-Isoprostane with stromal cell-derived factor-1 (SDF-1) and endothelial progenitor cell in nonhypertensive and hypertensive patients Wijaya, Johnson; Bakri, Syakib; Donosepoetro, Marsetio
Medical Journal of Indonesia Vol 19, No 2 (2010): May
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Aim Circulating endothelial progenitor cells (EPCs) are reduced in number and function in patients at risk for cardiovascular diseases. On the other hand, hypertension is related with excess angiotensin II which would lead to oxidative stress. In this study, we investigated the correlation between F2-Isoprostane (as marker of oxidative stress) with Stromal Cell-Derived Factor-1 (SDF-1) and CD34 viable in non hypertension and hypertension subjects.Methods This was a cross sectional study conducted on 54 non hypertension and 64 hypertension subjects visiting Prodia laboratory, Jakarta. F2-Isoprostane (as marker of oxidative stress) and SDF-1 (a strmal cell growth factor) were measured by ELISA method, and CD34 viable (marker of progenitor cell) was measured by flow cytometry.Results F2-Isoprostane concentration was higher in hypertensive subjects compared to non hypertensive subjects, although statistically non significant (mean + SD: 0.13 ± 0.120 vs 0.10 ± 0.16; ρg/mL; p = 0.091). SDF-1 concentration was significantly higher in hypertensive subjects compare to non hypertensive subjects (2821.63 ± 281.94 vs 2623.04 ± 356.28 ρg/mL; P < 0.05). CD34 viable level was significantly lower in hypertensive subjects compare to non hypertensive subjects (1.9 ± 0.9 /μL vs 2.7 ± 1.7; P < 0.05). F2-Isoprostane had negative correlation with CD34 viable in circulation (r = 0.022, p < 0.05) but no correlation with SDF-1 (p > 0.05).Conclusions F2-Isoprostane was higher, but CD34 was lower, in hypertensive subjects compared to non hypertensive. It seems that high F2-Isoprostane impaired the CD34 viable level as shown by negative correlation between F2- Isoprostane and CD34. (Med J Indones 2010; 19:109-12)Keywords: endothelial progenitor cell, F2-Isoprostan, hypertension, SDF-1
Proatherogenic or antiatherogenic high density lipoprotein type in acute coronary syndrome and healthy male person Kaniawati, Marita; Yusuf, Irawan; Bakri, Syakib; Santoso, Anwar
Medical Journal of Indonesia Vol 19, No 4 (2010): November
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Aim: To make proatherogenic/antiatherogenic HDL type criteria using Apolipoprotein A-I (ApoA-I), Paraoxonase-1 (PON-1), Neopterin and HDL-cholesterol levels, which may be useful in clinical practice.Methods: This was a case control study recruiting 52 subjects with Acute Coronary Syndrome (ACS) and 30 control healthy subjects. HDL type was classifi ed into antiatherogenic and  proatherogenic based on the levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol. Concentrations of ApoA-I was measured by immunoturbidimetry method, PON-1 was measured by colorimetric method, Neopterin was measured by ELISA, and HDL-C was determined by homogenous method. Univariate logistic regression analysis was done using ACS as a dependent variable and levels of ApoA-I, PON-1, Neopterin andHDL-cholesterol as independent variables. Proatherogenic/ antiatherogenic HDL type was determined by using ApoA-I, PON-1, Neopterin and HDL-cholesterol cut off and odd ratios.Results: Patient’s age was 50.89 + 12.63 year, HDL-C was 39.82 + 9.84 mg/dL, Apo A-1 was 119.77 + 32.05 mg/ dL, PON-1 was 41.26 + 18.19 kU/L, Neopterin was 16.22 + 38.10 nmol/L. Cut offs of ApoA-I, PON-1 and Neopterin successively were 124.5 mg/dL, 40.8 kU/L, and 7.016 nmol/L. On univariate logistic regression analysis showed that OR of ApoA-I, PON-1 and Neopterin respectively were 29.759 (95% CI : 4.074 – 217.382), 1.647 (95% CI : 0.412 – 6.586), 4.317 (95% CI : 1.098 – 16.977). Using scoring system, we concluded that total score > 18 was proatherogenic HDL type, and total score < 18 was antiatherogenic HDL type. With this scoring we found 78.85% had proatherogenic HDL type in ACS population.Conclusions: Dysfunctional HDL or proatherogenic/anti atherogenic  HDL type can be predicted by using ApoA-I– PON-1–Neopterin–HDL-cholesterol scoring system. Those with score of 18 are supposed to have antiatherogenic HDL type, and those with score of > 18 were having proatherogenic HDL type. (Med J Indones 2010; 19:228-34)Keywords: ApoliproteinA-I (ApoA-I), HDL-cholesterol, neopterin, paraoxonase-1 (PON-1), proatherogenic/antiatherogenic HDL
The Different Concentrations of Transforming Growth Factor-Beta1 (TGF-Beta1), Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) in Normoalbuminuria Normotension, Normoalbuminuria Hypertension Wijaya, Johnson; Donosepoetro, Marsetio; Bakri, Syakib
The Indonesian Biomedical Journal Vol 1, No 3 (2009)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Vascular remodeling was an adaptive process of the vascular wall that occured in response to long-term changes in hemodynamic conditions that contribute to the changes of the vascular structure and the pathophysiology of vascular disease. On the other hand, Endothelial Progenitor Cells (EPC) derived from bone marrow had the capacity to migrate to the peripheral circulation and to differentiate into mature endothelial cells. Therefore, EPC could contribute in the endothelial repairing after endothelial injury.METHODS: This study was a cross sectional design. Analysis was done among 30 subjects with normoalbuminuria normotension, 55 subjects with normoalbuminuria hypertension and 30 subjects with with microalbuminuria hypertension. TGF-β1, MMP-9 and VEGFR-2 testing were performed by ELISA method. All statistical calculations were performed using the SPSS 11.5 statistical software package. We used the Independent sample T test, Mann-Whitney, One Way Annova and Kruskal Wallis to establish the difference among various biochemical measures.RESULTS: TGF-β1 concentration was increased from normoalbuminuria normotension to normoalbuminuria hypertension and to microalbuminuria hypertension (27.63178±12.97246 vs. 38.61193±17.09546 vs. 38.73939±12.63911 ng/mL). TGF-β1 concentration was higher significantly in normotension as compared to hypertension (27.63178±12.97246 vs. 38.65692±15.58950, p<0.001) and to microalbuminuria hypertension (38.73939±12.63911, p<0.001). MMP-9 concentration was increased in normotension to normoalbuminuria hypertension but was decreased in microalbuminuria hypertension (438.1967±156.4268 vs. 564.5873±291.2876 vs. 418.6900±188.3801 ng/mL). MMP-9 concentration was higher significantly in normoalbuminuria hypertension as compared to microalbuminuria hypertension (p=0.028). VEGFR-2 concentration was decreased from normotension to normoalbuminuria hypertension to microalbuminuria hypertension (9.90552±1.85185 vs. 9.39561±1.75413 vs. 9.00506±1.47173 ng/mL). VEGFR-2 concentration was higher significantly in normotension as compared to microalbuminuria hypertension (p=0.042). CONCLUSIONS: The increasing concentration level of TGF-β1 and decreasing concentration level of MMP-9 in microalbuminuria hypertension showed that the remodeling process was getting increased. The decreasing concentration level of VEGFR-2 in microalbuminuria hypertension showed that the repairing process was getting decreased.KEYWORDS: vascular remodelling, vascular repairing, TGF-β1, MMP-9, VEGFR-2
The Analysis of Asymetric Dimethylarginine and Homocysteine in Patients with Chronic Kidney Disease Hendrawati, Tetty; Bakri, Syakib; Arif, Mansyur
The Indonesian Biomedical Journal Vol 1, No 2 (2009)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase (NOS). ADMA reduces NO synthesis when its concentration elevates. ADMA is a novel risk factor for cardiovascular disease. Plasma ADMA accumulates in patients with endstage renal disease, due to reduced renal clearance. Hyperhomocysteinemia is often found in patients with chronic kidney disease (CKD). Homocysteine may cause ADMA to accumulate; however, the mechanism by which ADMA level elevates in hyperhomocysteinemia is still unclear. Objective of this study was to analyze the concentrations of homocysteine and ADMA and to assess the correlation between homocysteine and ADMA concentrations with the severity of chronic kidney disease.METHODS: This was a cross-sectional study on 75 patients with CKD, comprising men and women aged 40-70 years. Assessments were done on the concentrations of creatinine, homocysteine, ADMA, fasting blood glucose, cholesterol HDL and triglyceride.RESULTS: In later stage of CKD there was significantly higher tHcy concentration as compared with the earlier stage of CKD (p=0.0000). In CKD stage 2 to 4 there was a tendency for ADMA concentration to increase to a significant average (p=0.210), but ADMA concentration was lower at stage 5. There was increased ADMA along with increased tHcy concentration of around 20μ mol/L, and this then decreased. The inverse correlation between tHcy and ADMA concentrations started to appear in CKD stage 4, but this correlation was statistically insignificant (r2 =0.19; p=0.499).CONCLUSIONS: This study showed there was a correlation between homocysteine and ADMA concentrations in patients with CKD stage 2 to 5, although statistically not significant.KEYWORDS: Asymetric Dimethylarginine, Homocysteine, Chronic Kidney Disease
Correlation between Systemic Arterial Hypertension and Bone Morphogenetic Protein-2 in Central Obese Non-Diabetic Men with Evidence of Coronary Artery Calcification Lukito, Antonia Anna; Widyasanto, Allen; Yulianti, Trilis; Muljadi, Rusli; Wijaya, Andi; Kabo, Peter; Bakri, Syakib
The Indonesian Biomedical Journal Vol 3, No 3 (2011)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Previous studies have confirmed separately the relationship between obesity, insulin-resistance, hypertension and bone morphogenetic protein-2 (BMP-2) with coronary artery calcification, a parameter of subclinical atherosclerosis. It was also reported that BMPs may function as proinflammatory, prohypertensive and proatherogenic mediators. The study aimed to assess the correlation between systemic hypertension and BMP-2 plasma concentration in central-obese non-diabetic men with evidence of coronary artery calcification.METHODS: This was a cross sectional study on 60 central-obese non-diabetic men, of an average age of 55.2 years, with evidence of coronary calcification, who came for health check-up and met the inclusion criteria consecutively as defined by waist circumference >90 cm and fasting blood glucose <126 mg/dL. Coronary calcification was defined by coronary artery calcium (CAC) score ≥10 Agatson-unit Dual Source 64 slice CT scan.RESULTS: There is positive correlation between hypertension and BMP-2 in central-obese non-diabetic men with evidence of coronary artery calcification. BMP-2 plasma concentration was higher in the hypertensive subjects. The correlation was stronger in younger (<55 years old) subjects and subjects with insulin-resitance.KEYWORDS: hypertension, BMP-2, coronary calcification, central obesity, age, insulin resistance
Correlation between Inflammation and Fibrinolysis in Hypertensive Centrally Obese Subjects: A Study on C-Reactive Protein, Plasminogen Activator Inhibitor-1 and Thrombin Activatable Fibrinolysis Inhibitor Sumiyati, Yati; Bakri, Syakib; Arif, Mansyur
The Indonesian Biomedical Journal Vol 4, No 3 (2012)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Hypertension and central obesity are risk factors of cardiovascular disease. Epidemiology studies have shown that these two conditions are closely linked and often occur simultaneously. Inflammation is an underlying pathomechanism in hypertension and obesity. Vascular inflammation is related to coagulation pathway, whereby high level of inflammation increases the risk of atherothrombosis event. The aim of this study was to investigate the correlation between inflammation and fibrinolysis in hypertensive centrally obese subjects compared with hypertensive non obese sbjects.METHODS: This was a cross sectional study conducted in October 2009-June 2010 involving 53 eligible subjects according to the following criteria: men or women aged 30-65 years, had neither diabetes (FPG <126 mg/dL and or OGTT <200 mg/dL) nor CKD (eGFR ≥60 mL/minutes). All subjects were not in an acute inflammation state, had no unspecific infection (hs-CRP ≤10 mg/L), or taking anti-inflammation or anti-hypertensive medication.RESULTS: In this study we found that the levels of hs-CRP (2.636 mg/L vs 1.024 mg/L, p=0.007), PAI-1 (43.58 ng/mL vs. 28.43 ng/mL, p=0.089) and TAFI (12.73 ng/mL vs. 12.19 ng/mL, p=0.479) were respectively higher in hypertensive subjects with central obesity than in hypertensive subjects with no central obesity. In hypertensive centrally obese subjects there was significant positive correlation between hs-CRP and PAI-1 (r=0.491, p=0.001) and TAFI (r=0.312, p=0.0390, meanwhile in hypertensive non-obese subjects significant correlation was found only between hs-CRP and TAFI (r=0.929, p=0.003).CONCLUSIONS: Obesity in hypertensive subjects has higher inflammation state that is correlated with fibrinolysis disruption.KEYWORDS: hypertensive, obesity, hs-CRP, PAI-1, TAFI
Inflammation is Associated with Vascular Remodeling - Repairing Balances in Hypertensive Obese Subjects Gantini, Lies; Bakri, Syakib; Wijaya, Andi; Santoso, Anwar
The Indonesian Biomedical Journal Vol 3, No 2 (2011)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Hypertension and obesity are proinflammatory conditions. Vascular remodeling is one of the pathomechanisms reflecting increased cardiovascular (CV) risks and represented as ratio of MMP-9 and sVEGFR-2 concentration. There is no association confirmed between inflammation and remodeling yet. This study was conducted to investigate the correlation between inflammation and vascular remodeling-repairing balances in hypertensive obese subjects.METHODS: This was a cross–sectional study recruited 34 hypertensive obese subjects and 10 hypertensive non obese subjects. They had no antihypertensive medications, neither diabetics nor renal disease and nor acute inflammation detected. Inflammation was assessed as increased hsCRP concentration. Vascular remodeling and repairing were consecutively represented by ratio of MMP-9 and sVEGFR-2.RESULTS: Concentration of hsCRP and MMP-9 were significantly higher in hypertensive obese group than non obese group (2.094±1.90 vs. 0.714±0.40 mg/L; p=0.029; 363.43±143.64 vs. 261.15±61.13 ng/mL, p=0.035, respectively), nonetheless no significant differences of sVEGFR-2 concentration (9.77±2.30 vs. 9.76±1.38 pg/mL, p=0.980) found in both groups. Ratio of MMP-9/sVEGFR-2 was significantly higher in hypertensive obese group than those in non-obese group (38.67±16 vs. 27.22±10, p=0.038). Likewise, they had more subjects with ratio of MMP-9/sVEGFR-2 ≥31.53. This figure is considered as cut-off point of vascular remodeling versus repairing.CONCLUSION: In hypertensive obese subjects, inflammation was activated and vascular remodeling more dominant than repairing process. Inflammation was associated with increased remodeling-repairing balances.KEYWORDS: Matrix Metalloproteinase-9 (MMP-9), soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2), high sensitivity C-Reactive Protein (hsCRP).
Altered Level of Soluble fms-like Tyrosine Kinase 1 (sFlt1) and Hypoxia Inducible Factor-1alpha (HIF-1alpha) in Normotensive Pregnancy and Preeclampsia Wantania, John; Bakri, Syakib; Pandelaki, Karel; Chalid, Maisuri
The Indonesian Biomedical Journal Vol 5, No 2 (2013)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Preeclampsia is still a significant problem worldwide. Of the many suggested mechanisms of its pathogenesis, the latest one is the balance of angiogenic factor and its relationship with hypoxia factors. The objective of this study was to observe changes or dynamic process of soluble fms-like tyrosine kinase 1 (sFlt1) as anti-angiogenic factor and hypoxia inducible factor 1-alpha (HIF-1α) as hypoxia marker in normotensive pregnancy and preeclampsia in mid-term and full-term pregnancies.METHODS: A cohort study was conducted on 36 normotensive subjects, first examination was conducted at 20-28 weeks of gestation. Then second examination was conducted at the time of preeclampsia diagnosed or full-term pregnancy. Preeclampsia was characterized by hypertension of systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, with two readings separated in 4-6 hours period, and/or proteinuria with urine dipstick of ≥1+ or ≥300 mg per 24 hours. Examinations of sFlt-1 and HIF-1α were done by enzyme-linked immunosorbent assay method. Statistical analysis was done using a significance level of p<0.05.RESULTS: Concentration of sFlt-1 was elevated in normotensive pregnancy and preeclampsia. Higher sFlt-1 concentration elevation was seen in preeclamptic group comparing to normotensive group, although not significant. This finding was related to the fact that investigated subjects were mostly developing mild preeclampsia merely. Comparing to normotensive group, preeclamptic group had higher HIF-1α concentration-per-week elevation, but not significant. There was a positive correlation between concentrations of sFlt-1 and HIF-1α, but not significant.CONCLUSION: sFlt-1 concentration elevation was correlated with preeclampsia. Therefore comparing to averages, changes of sFlt-1 concentrations were more important. Concentrations of HIF-1α and sFlt-1 were positively correlated.KEYWORDS: sFlt-1, HIF-1α, preeclampsia, normotension
Correlation between Homeostatic Model Assessment-estimated Insulin Resistance (HOMA-IR) with Asymmetric Dimethylarginine (ADMA) in Prehypertension Novianti, Maria Evi; Bakri, Syakib; Arif, Mansyur; Sandra, Ferry
The Indonesian Biomedical Journal Vol 5, No 3 (2013)
Publisher : The Prodia Education and Research Institute (PERI)

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Abstract

BACKGROUND: Not only hypertension, prehypertension has been reported to be linked with increased cardiovascular morbidity and mortality risks as well. Prehypertension has three-fold hypertension and two-fold cardiovascular risks. Pathomechanism that links hypertension with cardiovascular is related with endothelial dysfunction and insulin resistance. Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas shown by asymmetric dimethylarginine (ADMA). Subjects with prehypertension had higher insulin resistance events than normotension, whereas shown by homeostatic model assessment-estimated insulin resistance (HOMA-IR). This research was conducted to investigate the correlation of HOMA-IR with ADMA in prehyper- and normo-tension.METHODS: A cross-sectional comparative research was designed. Subjects were recruited and divided into prehyper- and normo-tensive groups. ADMA was measured using ELISA method, while HOMA-IR was calculated by the ratio of fasting insulin and glucose. Spearman 1-tail and Mann Whitney statistical analyses were performed.RESULTS: Comparing to normotensive group, elevated levels of HOMA-IR and ADMA in prehypertensive group were shown, but not significant. In prehypertensive group, we found significant correlation between HOMA-IR and ADMA.CONCLUSION: Insulin resistance and endothelial dysfunction was elevated in prehyper-compared to normotension.KEYWORDS: prehypertension, insulin resistance, endothelial dysfunction, HOMA-IR, ADMA
Role of 8-isoprostane, Matrix Gla Protein (MGP) and Bone Morphogenetic Protein-2 (BMP-2) in Vascular Calcification in Chronic Kidney Disease Rositawati, Wiwik; Bakri, Syakib; Lawrence, Gatot Susilo; Wijaya, Andi
The Indonesian Biomedical Journal Vol 5, No 2 (2013)
Publisher : The Prodia Education and Research Institute (PERI)

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BACKGROUND: Vascular calcification may be an important risk factor of cardiovascular disease in Chronic Kidney Disease (CKD). The pathobiology of vascular calcification in CKD is complex and involves some factors including inflammation, oxidative stress and balancing of calcification regulators. The aim of the study was to investigate the interaction between 8-isoprostane with calcification regulators such as matrix gla protein (MGP) and bone morphogenetic protein (BMP)-2 with vascular calciication in CKD.METHODS: A cross-sectional study was performed on 63 subjects undergoing haemodialysis maintenance for more than 3 months. Abdominal aortic calcification (AAC) was measured using a lateral abdominal X-ray for calcification in abdominal aorta, which is related to severity of calcific deposits at lumbar vertebral segment (L)1-L4. Serum levels of 8-isoprostane, MGP and BMP-2 were measured by enzyme-linked immunosorbent assay method.RESULTS: Results showed that 8-isoprostane levels were correlated with BMP-2 (r=0.266, p=0.018) and MGP levels (r=0.410, p≤0.001). MGP/BMP-2 levels ratio was correlated with AAC score (r=0.279, p=0.013). Subjects were then stratified into 3 groups based on AAC score: 0, 1-6 and ≥7. The highest mean of MGP levels was in AAC score 1-6 group, and the highest mean of 8-isoprostane levels was in AAC score ≥7. In the group of AAC score 0, 8-isoprostane levels were correlated with MGP levels (r=0.499, p=0.001) and MGP/BMP-2 levels ratio (r=0.291, p=0.034). In AAC score 1-6 group, 8-isoprostane levels were correlated with BMP-2 (r=0.661, p=0.005) and MGP levels (r=0.569, p=0.017). In AAC score ≥7 group, MGP levels were positively correlated with AAC score (r=0.608, p=0.041). With multivariate logistic regression analyses, we identified that increased MGP/BMP-2 levels ratio (OR=12.436; 95% CI=1.595-96.971) was an independent predictor in aortic calcification event.CONCLUSION: We concluded that regulators of calcification including calcification inhibitor and promoter related to oxidative stress, were associated with vascular calcification in CKD. MGP levels were increased in the early of calcification and MGP/BMP-2 levels ratio was a strong predictor for vascular calcification in CKD.KEYWORDS: vascular calcification, CKD, oxidative stress, 8-isoprostane, MGP, BMP-2