The Indonesian Biomedical Journal

4-23

Authors: Anna Meiliana, Andi Wijaya

BACKGROUND: The discovery of endothelial progenitor cell (EPC) a decade ago by Asahara, et al has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The reduced circulating concentration of EPCs is a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases. CONTENT: Diabetes is linked to impaired vascular function, including alterations in both endothelial cells and EPCs. A number of studies have shown that individuals with diabetes have decreased level of circulating EPCs and that the severity of disease is inversely proportional to EPC levels. In vitro, hyperglycemia increases the rate of EPC senescence and the angiogenic function of EPCs from patients with either type 1 or type 2 diabetes is impaired such that they are poorly proliferative and fail to incorporate into forming vessel-like structures. Given the comprehensive role of EPC alterations in diabetes complications, modulation of the levels and/or function of EPCs may be considered a potential therapeutic strategy. SUMMARY: The available data demonstrating that decrease or dysfunction of EPCs may have a prominent role in the pathogenesis of all diabetes complications. Further approaches, such as EPC administration, may represent novel treatments for diabetic vasculopathy in the future. To date, many barriers remain to such a therapeutic approach. Firstly, there is no specific marker for EPC at present. Secondly, techniques of EPC isolation are not standardized, preventing direct comparison between various studies. The long-term effects of transplanted EPCs are currently unknown.

31-7

Authors: Yani Lina, Gatot Susilo Lawrence, Andi Wijaya

BACKGROUND: The prevalence of obesity has increased dramatically in recent years. It is commonly associated with type 2 diabetes, coronary artery disease, and hypertension. White adipose tissue (WAT) is a major site of energy storage and is important for energy homeostasis. WAT has been increasingly recognized as an important endocrine organ that secretes a number of biologically active “adipokines”. The resultant higher FFA, FABP4, FABP5 concentration; and lower concentration of adiponectin is known to be correlated with inflammation. The aim of this study was to observe the correlation between FFA, FABP4, FABP5 and adiponectin with TNF-α and Interleukin-6 as markers of inflammation. METHOD: The study was observational with a cross sectional design. The analysis was done on 69 male subjects aged 30-60 years with non diabetic abdominal obesity which is characterized by waist circumference (WC) 98.7 ± 6.5 cm and fasting blood glucose 87.1 ± 9.7 mg/dL. FFA testing was performed by enzymatic colorimetric assay; whereas FABP4, FABP5, TNF-α, adiponectin and IL-6 were performed by ELISA. All statistical calculations were performed with the SPSS 11.5 statistical software package. We used the Pearson or Spearman’s rho correlation coefficient to assess the correlation between various anthropometric and biochemical measures. We also used path analysis Lisrel 8.30 for Windows. RESULT: This study revealed that there was no correlation between FFA, FABP4 and adiponectin with TNF-α and Interleukin-6, whereas there was correlation between FABP5 with TNF- and Interleukin-6. This study also showed there were correlations between WC and hsCRP (r = 0.314, p = 0.000), WC and IL-6 (r = 0.276, p = 0.022), FFA and FABP4 (r = 0.263, p = 0.029), FABP4 and WC (r = 0.249, p = 0.039), FABP4 and BMI (r = 0.311, p = 0.009), FABP5 and TNF- (r = 0.408, p = 0.000), FABP5 and FABP4 (r = 0.296, p = 0.014), FABP5 and Interleukin-6 (r = 0.248, p = 0.04), Adiponectin and HDL-Cholesterol (r = 0.301, p = 0.012). CONCLUSION: Abdominal obesity might contribute to inflammation in obese nondiabetic males. This study indicated that in abdominal obesity, FFA may induce inflammation through FABP4 and FABP5. Advancing our understanding of the function and measurement of FABP4 and FABP5 serum concentration will give insight into the clinical diagnosis of obesity-related metabolic disorders.

45-50

Authors: Mona Yolanda, Marsetio Donosepoetro, Anwar Santoso

BACKGROUNDS: Heart failure, a new epidemic of cardiovascular disease, has become an important issue and its prognosis is poor. Heart failure is the condition where the impaired heart cannot pump enough blood to provide the needs of metabolic tissues and organs. Early diagnosis of heart failure is really crucial to determine the success of treatment and to prevent further myocardial dysfunction and worsening clinical symptoms. This condition can be worsened by ET-1, which triggers the secretion of IL-6 and TNF-α as pro inflammation factors. In Systolic Heart Failure, systolic function changes are accompanied by changes in diastolic function. Thus, the condition of systolic heart failure is worse than Diastolic Heart Failure. The purpose of this study is to assess the relationship of ET-1 with diastolic and systolic heart failure groups and the relationship of ET-1 with TNF-α and IL-6 as pro inflammation factors. METHODS: The design of this study was cross-sectional analysis on 62 patients with heart failure, grouped according to the classification of diastolic and systolic heart failure. RESULTS: A significant positive correlation of ET-1 with diastolic and systolic heart failure was found (p = 0.008; r = 0.324). A significant positive correlation was also found between ET-1 and IL-6 (p = 0.001; r = 0.393), but a less significant correlation was noted between ET-1 and TNF-α (p = 0.201; r = -0.158). CONCLUSIONS: ET-1 has the strongest correlation (p=0.033) with prevalence ratio 3.930 and can differentiate between Diastolic and Systolic Heart Failure.

59-63

Authors: Tommy Heryantho, Andi Wijaya, Teguh Santoso

BACKGROUND: Thrombus is a main cause of cardiac death. Therefore identifying which coronary artery plaque is vulnerable to rupture is a critical step for cardiac intervention to prevent future cardiac events. Systemic biochemical markers are used for predicting rupture of coronary plaque or identifying stenotic coronary artery plaque(s) vulnerable to rupture. METHODS: Blood samples of 2 x 24 locations (2 x 10 controls, 2 x 12 stable plaques and 2 x 2 unstable plaques) of 13 patients to undergo stent placement were taken from an artery which showed no stenosis (control), 70% or more stenosis of stable plaques and unstable plaques, respectively. The blood samples were taken by using micro-catheter distally and proximally. Concentrations of MPO, MMP-9, SPLA2 and CD40L of each sample were assayed. RESULTS: Concentration of MMP-9 in unstable coronary artery plaque (94.7 + 14.4 ng/ml) significantly increased compared with that of stable coronary artery plaque (71.0 + 67.8 ng/ml, p=0.024). SPLA2 concentration significantly decreased in unstable coronary artery plaque (45.9 + 14.0 pg/ml) compared with that of stable coronary artery plaque (80.9 + 39.3 pg/ml, p=0.015). Nine of ten studied subjects showed an average of 14.5% (range: 0.0 – 28.8%) decrease of the SPLA2 concentration in stable plaques compared with that of the non-stenotic coronary artery. CONCLUSION: MMP-9 increased in unstable coronary artery plaque compared with that of stable coronary plaque. Unstable coronary artery plaques absorbed SPLA2 from the vasculars more than the stable plaques and control plaques. MMP-9 and SPLA2 may be used as markers of stability of a plaque in coronary artery in relation to its rupture potential.