The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Correlation between Homeostatic Model Assessment-estimated Insulin Resistance (HOMA-IR) with Asymmetric Dimethylarginine (ADMA) in Prehypertension
Get PDFBACKGROUND: 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, ADM
Vascular Stem Cells in Vascular Remodeling and Diseases
Get PDFBACKGROUND: Blood vessels are a source of stem and progenitor cells, which likely contribute to a variety of vascular processes and diseases. Emerging concepts in this field could influence therapeutic approaches to diseases of blood vessels such as atherosclerosis.CONTENT: Vascular Stem Cells (VSCs) field is only beginning to emerge, and thus, many issues regarding VSCs’s identity and function remain poorly understood. In fact, even after decades of intensive research, Mesenchymal Stem Cells (MSC), which is suggested to be VSCs, is still having many outstanding issues of its own. And, on top of this, likewise decades-long intensive pericyte research has not been able resolve the identity issue. While favors Adventitial Progenitor Cells (APCs) over pericytes as the likely VSC candidate, it should be pointed out that currently the opposite view (i.e., pericytes as VSCs) is more prevalent, and many excellent reviews, including a recent one, have discussed this issue extensively.SUMMARY: It has been postulated that, within the vasculature, APCs could differentiate into pericytes (CD34- CD31- CD140b+ SMA-), endothelial cells (CD34+ CD31+ CD140b- SMA-), and smooth muscle cells (SMCs) (CD34- CD31- CD140b- SMA+); and during tissue expansion or repair, APCs could also differentiate into tissue-specific cell types (e.g., muscle and fat) Thus, in vitro, APCs fulfill all criteria for being VSCs. Meanwhile, in vivo evidence is still limited and will require further investigation.KEYWORDS: vascular stem cells, VSC, mesenchymal stem cells, MSC, endothelial progenitor cells, EPC, adventitial progenitor cells, AP
Study of Low-grade Chronic Inflammatory Markers in Men with Central Obesity: Cathepsin S was Correlated with Waist Circumference
Get PDFBACKGROUND: There is a prevalence increase of overweight and obesity in Indonesia. Central obesity can lead a variety of chronic diseases through the inflammatory process. There are some markers for low-grade chronic inflammatory, such as cathepsin S, high sensitivity C-reactive protein (hs-CRP), interleukin-1- beta (IL-1β). To our current interest that central obesity can lead to various chronic diseases through the inflammatory process, we conducted a study to investigate correlation of Cathepsin S, hs-CRP, IL-1β in men with central obesity.METHODS: A cross-sectional study was conducted. Seventy-eight selected subjects were examined to collect anthropometric data and prepared for sample collection. Collected samples were processed for the following biochemical analyses: fasting glucose, high density lipoprotein (HDL)-cholesterol, triglyceride, serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), cathepsin S, hs-CRP, and IL-1β. Data distribution and variable correlation were then statistically analyzed.RESULTS: There were significant correlations between waist circumference (WC) and cathepsin S (p=0.030; r=0.214), hs-CRP and cathepsin S (p=0.007; r=0.276), triglyceride and IL-1β (p=0.019; r=-0.235), WC and systolic blood pressure (SBP) (p=0.003; r=-0.312), WC and fasting glucose (p=0.000; r=0.380), WC and body mass index (BMI) (p=0.000; r=0.708).CONCLUSION: Our study showed that cathepsin S was correlated with central obesity, suggesting that cathepsin S could be a potential inflammatory marker in central obesity in the future.KEYWORDS: obesity, inflammation, hs-CRP, cathepsin S, IL-1β, waist circumferenc
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
No full textBACKGROUND: 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, TAF
Inflammation and Atherosclerosis: Current Pathogenesis
No full textBACKGROUND: The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown.CONTENT: Chronic inflammation is recognized as a major driving force in atherogenesis. The sites of atherosclerotic plaque development in the arterial wall are characterized by cholesterol accumulation and infiltration of peripheral blood monocytes, which gradually differentiate into macrophages. Cholesterol crystals, the common constituents of atherosclerotic lesions, include NLRP3 inflammasome activation and IL-1β secretion in human macrophages, promote an inflammatory milieu and thus drive lesion progression. Consequently, the cholesterol crystal-induced inflammasome activation may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions. SUMMARY: The crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. The cholesterol crystal-induced inflammasome activation in macrophages may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions. This finding provides new insights into the pathogenesis of atherosclerosis and indicates new potential molecular targets for the therapy of this disease.KEYWORDS: atherosclerosis, inflammation, neutrophil, macrophages, inflammasome, cholesterol crysta
The Correlation between Lipoprotein-Associated Phospholipase A2 and Atherosclerosis (ox-LDL) in Centrally Obese Men
No full textBACKGROUND: Obesity is closely associated with atherosclerosis. Obesity and atherosclerosis are closely associated with inflammatory disease. Atherosclerosis constitutes a multifactorial disorder affecting the arterial wall, which is initiated by dyslipidemia and excerbated by inflammation. Plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and oxidized low density lipoprotein (ox-LDL) have been identified as risk factors for cardiovascular disease. Lp-PLA2 is the sole enzyme responsible for the hydrolysis of oxidized phospholipids (oxPL) on LDL particles in atherosclerosis plaque. Plasma level of oxLDL is associated with inflammation and plays an important role in the development of atherosclerosis. The aim of this study was to assess the correlation between Lp-PLA2 and atherosclerosis (oxLDL) in centrally obese men.METHODS: This was a cross-sectional study involving 71 men with central obesity with waist circumference >90 cm, aged 30-60 years old. Lp-PLA2 measurement was done by sandwich enzyme immunoassay. oxLDL measurement was done by ELISA method. RESULTS: Results of this study showed that central obesity correlated positively with oxLDL (r=0.258; p=0.040) and Lp-PLA2 >422 ng/mL correlated positively with oxLDL (r=0.331; p=0.042).CONCLUSIONS: We conclude that there is a correlation of Lp-PLA2 with atherosclerosis (oxLDL) in men with central obesity.KEYWORDS: obesity, Lp-PLA2, oxLDL, atherosclerosi
The Role of Signal Transducer and Activator of Transcription 3 (STAT3) in Tumor Immunity
No full textBACKGROUND: Inflammation is a key component of the tumor microenvironment. Cancer-associated inflammation is marked by the presence of specific inflammatory cells and inflammatory mediators. Moreover, immune cells in the tumor microenvironment not only fail to mount an effective antitumor immune response, but also interact intimately with the tumor cells to actively promote oncogenesis.CONTENT: Their roles in regulating cytokine-dependent inflammation and immunity make the signal transducer and activator of transcription (STAT) proteins critical players in determining whether immune responses in tumor microenvironment promote or inhibit cancer. Recent evidence suggests a crucial role for STAT family proteins, especially STAT3 (signal transducer and activator of transcription 3), which is a point of convergence for numerous oncogenic signaling pathways, in selectively inducing and maintaining a procarcinogenic inflammatory microenvironment, both at the initiation of malignant transformation and during cancer progression. The persistent activation of STAT3 increases tumor cell proliferation, survival, and invasion while supressing antitumor immunity. SUMMARY: STAT3 signaling pathway constitutes a potential preventive and therapeutic target for cancer immunotherapy. KEYWORDS: STAT3, inflammation, tumor microenvironment, cancer immunotherap
Novel Sources of Fetal Stem Cells for Future Regenerative Medicine
No full textBACKGROUND: Mesenchymal stromal cells are multipotent cells considered to be of great promise for use in regenerative medicine. However, the cell dose may be a critical factor in many clinical conditions and the yield resulting from the ex vivo expansion of mesenchymal stromal cells derived from bone marrow may be insufficient. Thus, alternative sources of mesenchymal stromal cells need to be explored.CONTENT: There are multiple extra-embryonic tissues emerging during gestation including umbilical cord blood (UCB), amniotic fluid (AF), Wharton’s jelly, the amniotic membrane and the placenta, which are all discarded following birth. Fetal stem cells from these sources actually represent a new class of stem cells developmentally and operationally located between the state of embryonic stem cells and adult stem cells, sharing and exhibiting features of pluripotency and multipotency, without necessarily implying that they can generate every type of tissue.SUMMARY: Fetal stem cells have been recently isolated from several tissues (amniotic fluid, umbilical cord, Wharton’s jelly, amnion and placenta). They are derived either from the fetus proper or from the supportive extra-embryonic structures. They represent ideal sources for regenerative medicine since they are easily accessible, exhibit high proliferation rates, do not form teratomas and present no ethical reservations like embryonic stem cells (ESC). Their functional features indicate that they actually represent intermediates between ESC and adult stem cells.KEYWORDS: mesenchymal stem cells, fetal stem cells, amniotic fluid, umbilical cord, placenta, wharton’s jell
Comparison of the Effects of Three Extract Sorts of Soybean DETAM 1 on the Total Cholesterol Level in Balb-C Male Mice
No full textBACKGROUND: Hypercholesterolemia is a major risk factor for coronary heart disease. Pharmacological treatment of hypercholesterolemia are known to have side effects, hence the need for an alternative medicine, like herbal medicine, such as soybean as an example. Research objective is to compare the effects of ethanol extract, protein extract, and ethyl acetate fraction of soybean tempeh Detam-1 on the total serum cholesterol level of male mice.METHODS: This study was a laboratory experimental study with Completely Randomized Design (CRD) method. Twenty five balb-C strain male mice were allocated into five groups, namely: the negative-control (aquabidest), the positive-control (simvastatin), ethanol extract, protein extract and ethyl acetate fraction of the soybean tempeh Detam-1 and all were fed with high cholesterol containing food for 31 days. Starting on the 18th day all groups were treated for 14 days. The observed parameter was the total serum cholesterol level. The data of the study results were analyzed with ANOVA, followed by Tukey HSD test.RESULTS: There were significant differences between treatment groups and the negative-control (p=0.004). The reduction of the total cholesterol level of soy ethanol extract was 35.11±15%, the ethyl acetate fraction of soybean tempeh 26.48±17%, and soy protein extract was 15.33±33.1%, and no significant difference was noted in the positive-control group (simvastatin). CONCLUSION: The ethanol extract of soybean seed, protein extract of soybean seed, and ethyl acetate fraction of soybean tempeh Detam-1 have the same effect as do simvastin, and ethanol extract of soybean seed is the most effective substance for lowering total serum cholesterol in Balb-C male mice.KEYWORDS: hypericholesterolemia, ethanol extract, protein extract and ethyl acetate fraction, soybean Detam-1
Association Between Cathepsin S, Cystatin C and High Sensitivity C-Reactive Protein (hsCRP) with Oxidized LDL (Ox-LDL) in Men with Central Obesity
No full textBACKGROUND: Inflammation is a central feature of the atherosclerotic process particularly in obesity. hsCRP, a marker of inflammation, may be directly involved in all phases of atheroslerosis by complement activation, apoptosis, vascular cell activation, monocyte recruitment, lipid accumulation and thrombosis. Inflammation has a causal relationship with cysteine proteases including cathepsin S. Therefore, cathepsin S is considered as a molecular link between obesity and atherosclerosis. An imbalance between elastolytic cysteine proteases, cathepsin S and its inhibitor, cystatin C, is involved in the pathogenesis of atherosclerosis. Some studies have shown that increased circulating levels of cathepsin S, hsCRP and cystatin C in inflammatory conditions contribute to atherosclerosis. This study was conducted to investigate the associations between ox-LDL and cathepsin S, and cystatin C and hsCRP in men with central obesity.METHODS: This was a cross-sectional study involving 71 male subjects with central obesity (waist circumference ≥90 cm), with no renal dysfunction, aged 30-60 years.RESULTS: Cathepsin S did not have a significant correlation with ox-LDL (r=0.158, p=0.096). ox-LDL had positive correlation with cystatin C (r=0.156; p=0.029) and hsCRP (r=0.204; p=0.045), and cathepsin S/cystatin C ratios (r=0.360; p=0.024) at level >91 U/L (median ox-LDL).CONCLUSIONS: There were associations between ox-LDL and cystatin C, hsCRP and cathepsin S/cystatin C ratios in men with central obesity.KEYWORDS: obesity, inflammation, atherosclerosis, hsCRP, cystatin C, cathepsin S, ox-LD