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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 1  |  Page : 8-12

Evaluation of chemerin in acute coronary syndrome and its role in cardiodiabetics


1 Department of Pathology, M.L.N. Medical College and Associated S.R.N Hospital, Prayagraj, Uttar Pradesh, India
2 Cardiology, M.L.N. Medical College and Associated S.R.N Hospital, Prayagraj, Uttar Pradesh, India

Date of Submission23-Jun-2020
Date of Decision06-Sep-2020
Date of Acceptance17-Sep-2020
Date of Web Publication27-Mar-2021

Correspondence Address:
Dr. Anshul Singh
Department of Pathology, M.L.N. Medical College and Associated S.R.N Hospital, George Town, Prayagraj - 211 001, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCPC.JCPC_45_20

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  Abstract 


Objectives: Chemerin is a proinflammatory adipokine whose role in metabolic syndrome and insulin resistance is well known. Chemerin has shown to carry a good prognostic/predictive value in patients of Coronary Artery Diseases (both chronic as well as acute) in the studies done in the US and Europe. However, no such study has been reported from India. Hence, this study was undertaken to evaluate Chemerin in patients of Acute Coronary Syndrome (ACS) and assess their role in cardiodiabetic patients. Materials and Methods: We included seventy cases of ACS and further subdivided them into two groups - (1) with co-existing diabetes mellitus (ACS-DM) (n = 33) and (2) without co-existing DM (ACS-NDM) (n = 37). Thirty healthy age and sex matched controls were included for comparison. Chemerin levels were measured by ELISA, hs C Reactive Protein (hs CRP) by turbidimetric assay, Creatine Kinase MB (CK-MB) by immunoinhibition (IFCC method) and Troponin I (Trop I) by Chemiluminescent Microparticle immunoassay. All the data were analyzed using Social Science Statistics Calculators. Results: Serum Chemerin levels were highest in ACS-DM (0.80 ± 0.61 ng/ml) as compared to ACS-NDM (0.42 ± 0.22 ng/ml) and controls (0.25 ± 0.10 ng/ml). On comparison, the difference amongst all was statistically significant. Furthermore, Chemerin showed a positive correlation with all the three parameters of ACS – hs CRP, CK- MB and Trop I. Conclusion: Chemerin levels are markedly elevated in ACS patients, more so in those with coexisting diabetes [cardio diabetics]. Chemerin is a novel biomarker of ACS.

Keywords: Adipokines, coronary artery disease, hyperglycemia, microinflammation


How to cite this article:
Kumar M, Prajapati R, Saxena P, Singh A, Misra V. Evaluation of chemerin in acute coronary syndrome and its role in cardiodiabetics. J Clin Prev Cardiol 2021;10:8-12

How to cite this URL:
Kumar M, Prajapati R, Saxena P, Singh A, Misra V. Evaluation of chemerin in acute coronary syndrome and its role in cardiodiabetics. J Clin Prev Cardiol [serial online] 2021 [cited 2021 Apr 21];10:8-12. Available from: https://www.jcpconline.org/text.asp?2021/10/1/8/312223




  Introduction Top


Adipose tissue is considered as an active endocrine organ that secrets a number of bioactive mediators known as adipokines.[1] Chemerin is a relatively newly discovered adipokine which is also known as Tazarotene-Induced Gene 2.[2] It was initially documented in psoriatic skin lesions.[3] Subsequently with ongoing researches, its role in different conditions has been observed. As a proinflammatory adipokine, Chemerin plays a very important role in microinflammation that forms the core etiopathogenesis of many diseases including obesity, metabolic syndrome, insulin resistance, diabetic micro and macroangiopathies, chronic kidney diseases, and cardiovascular diseases.[4],[5],[6]

A definite role of Chemerin in chronic Coronary Artery Diseases (CAD) has been documented in many research papers studying various associated parameters such as arterial stiffness, brachial artery pulse wave velocity, and atherosclerotic plaque burden.[7],[8] However, its role in Acute Coronary Syndromes (ACSs) has not been very well elucidated. One reason for this is the comparatively fewer studies done and second is that the results of these studies have been somewhat inconsistent with some studies seeing no association,[9] whereas others observing it to have an independent role in prediction of ACS.[10],[11]

Interestingly, a few studies done on cardiodiabetic patients (those who are suffering from CADs and are diabetic as well) have reported it to be an important predictive marker of acute coronary events,[12],[13] some even considering it to be as significant as hs C Reactive Protein (hs-CRP).[14],[15]

In India, where CADs constitute a major proportion of the health burden, studies evaluating the role of Chemerin in such patients are lacking. Keeping this in mind, we aimed to assess serum Chemerin in patients of ACS, both with Diabetes (Cardio diabetics) and without Diabetes (Non diabetics) and also attempted to correlate it with other parameters of ACS namely hs-CRP, Creatine Kinase MB (CK-MB) and Trop-I.


  Materials and Methods Top


This study was conducted in the department of Pathology in collaboration with the department of Cardiology over a period of 1 year. This study was approved by the institutional ethical committee.

Case selection

A total of 70 cases were included in this study after taking proper and willful consent for participation. Cases selected were those who were admitted to intensive care unit with complaints of acute unremitting chest pain and were diagnosed as ACS on the basis of physical examination along with the finding of either a significant increase of Troponin I (Trop-I)/CK-MB levels or ST-segment changes as seen in the electrocardiogram (ECG).

These cases were further divided into two groups:

Acute coronary syndrome with co-existing diabetes mellitus

Here, those patients were included who were either.

  1. Already known cases of Type 2 Diabetes Mellitus (DM) but not on insulin therapy


  2. Or

  3. Who had RBS value ≥200 mg/dl along with the cardinal symptoms of hyperglycemia.


(Mentioned as one of the Diabetes defining criteria in the guidelines issued by the American Diabetes Association [ADA]).[16]

Acute coronary syndrome without co-existing diabetes mellitus

Those included in group II were neither known cases of Type 2 DM nor they met the ADA criteria for hyperglycemia at the time of inclusion in the study.

All individuals included in this study were subjected to extensive history taking focusing on Type 2 DM, hypertension, and pattern of chest pain on physical activity/rest followed by a detailed physical examination.

Inclusion criteria

Patients presenting with acute chest pain even on rest along with either typical ECG changes or elevated cardiac markers (CK-MB/Trop I). There was no age restriction.

Exclusion criteria

Those patients with ACS were excluded who had one of the following diseases:

  • Valvular heart disease
  • Thromboembolic episodes
  • Any Collagen vascular diseases
  • Advanced liver disease (MELD score >40)
  • Renal failure (e GFR <60 ml/min/1.73 m2)
  • Any malignancy in the past or present
  • On Insulin therapy.


Control group

Thirty age and sex matched controls who were apparently healthy attendants of the patients were included after proper history taking ruling out for hypertension, hyperglycemia, and cardiac problems in particular. Proper and willful consent for participation in this study was obtained from all of them.

Samples from all the cases and controls were collected in plain vial, centrifuged at 3000 rpm for 15 minutes and serum was separated and stored at −20° C for further use.

Methodology used

Serum Chemerin

Human CHEM (Chemerin) ELISA kit (Catalog No: E-EL-H0698) from Elabscience, USA was used.[17]

  • Detection Range: 0.16–10 ng/ml
  • Coefficient of Variation: <10%.


Hs C reactive protein

LAB KIT-hs CRP Turbilatex quantitative turbidimetric test (CHEMELEX, SA-Barcelona) was used.[17]

  • Detection Range: nonreproducible results in values <1 mg/L
  • Linearity Range: up to 150 mg/L.


Creatine kinase-MB

The estimation was done using CK-MB SL kit by ELITech Clinical Systems SAS, France, that used the Immuno-inhibition method (IFCC).

Principle CK MB SL reagent contains an antibody inhibiting specifically CK-M subunits (i.e., 100% of CK-MM and 50% of CK-MB isozymes). The remaining activity, corresponding to CK-B fraction activity, is measured according to the IFCC reference method for measuring CK activity. CK-MB activity is then obtained by multiplying by 2 the remaining activity.

Calculation:

Activity (U/L) = △A/min × 8254 (At 340 nm, with a 1 cm light path cuvette)

Reference Values: 0–25 U/L

Measuring Range: 15–600 U/L.

Troponin I

Architect STAT high Sensitive Troponin-I assay by Abbott Diagnostic division Lisnamuck, Longford, Ireland was used. It is a Chemiluminescent Microparticle immunoassay (CMIA).

Principle-The Architect STAT High Sensitive Troponin-I assay is a two-step immunoassay to determine the presence of cardiac Trop I (cTnI) in human plasma and serum using CMIA technology with flexible assay protocols, referred to as Chemiflex.

Procedure

  1. Sample and anti-Trop I antibody coated paramagnetic microparticles are combined. The cTnI present in the sample binds to the anti-Trop I coated microparticles
  2. After incubation and washing, anti-Trop I acridinium- labeled conjugate is added to create a reaction mixture
  3. Following another incubation and wash cycle, Pre-trigger and Trigger solutions are added to the reaction mixture
  4. The resulting chemiluminescent reaction is measured as relative light units (RLU'S).


The concentration of cTnI is read relative to a standard curve established with calibrators of known cTnI concentrations.

Detection range: 10–50,000 pg/ml

Coefficient of Variation: <10%.

Statistical analysis

All the data were expressed as Mean ± standard deviation (SD) and analyzed using MedCalc Software Ltd Acacialaan 22 8400 Ostend Belgium GraphStats, Bengaluru, Karnataka, India. ANOVA with Bonferroni corrections was used to assess the significance of difference in the levels of Chemerin in different groups (Controls, ACS-NDM and ACS-DM).The correlation analysis between serum Chemerin levels and other measured parameters was performed by Pearson correlation coefficient test using Social Science Statistics Calculators. P < 0.05 was uniformly accepted as significant.


  Results Top


Controls

It comprised of 20 males and 10 females (M: F = 2:1) with mean (SD) age of 59.87 ± 5.88 years.

The mean (SD) RBS level was 126.06 ± 48.79 mg/dl.

The mean (SD) hs-CRP level was. 30±0.10 mg/L.

The mean (SD) Chemerin level was 0.25 ± 0.10 ng/ml.

Acute coronary syndrome without co-existing diabetes mellitus

It comprised of 31 males and 6 females (M: F = 5.1:1) with mean (SD) age of 61.35 ± 9.49 years.

The mean (SD) RBS level was 128.92 ± 26.99 mg/dl.

The mean (SD) hs-CRP level was 4.03 ± 1.92 mg/L.

The mean (SD) Chemerin level was .42 ± 0.22 ng/ml.

The mean (SD) CK–MB level was 117.24 ± 112.91 U/L.

The mean (SD) Trop–I level was 6217.39 ± 5533.18 pg/ml.

Acute coronary syndrome with co-existing diabetes mellitus

It comprised of 23 males and 10 females (M:F = 2.3:1) with mean (SD) age of 59.06 ± 9.12 years.

The mean (SD) RBS level was 245.33 ± 67.32 mg/dl.

The mean (SD) hs-CRP level was 8.04 ± 1.2 mg/L

The mean (SD) Chemerin level was .80 ± 0.61 ng/ml.

The mean (SD) CK–MB levels were 216.42 ± 189.57 U/L.

The mean (SD) Trop I levels were 17608.5 ± 16151.7 pg/ml.

Comparison of Serum hs CRP, Chemerin, CK MB and Trop I:

Levels of all the four assessed parameters, i.e., hs CRP, Chemerin, CK-MB and Trop–I were highest in ACS-DM group as compared to ACS-NDM and controls. On comparison, the difference among the groups was statistically significant for all the four [Table 1].
Table 1: Comparison of key laboratory findings in controls, ACS - NDM and ACS - DM patients

Click here to view


Correlation of Chemerin with hs CRP, CK MB and Trop I:

Correlation analysis of Chemerin with hs-CRP, CK-MB, and Trop-I in all the cases of ACS-NDM group and ACS–DM group showed a positive result with all the three parameters in both the groups. However, this was found to be significant only with hs-CRP and Trop-I in both the groups, whereas with CK-MB the correlation was not statistically significant in either of the groups [Table 2].
Table 2: Correlation of chemerin with hs-C-reactive protein, creatine kinase MB and Trop-I in acute coronary syndrome nondiabetic and acute coronary syndrome with diabetes mellitus patients

Click here to view



  Discussion Top


Chemerin is a novel adipokine that is a potent chemoattractant for cells that express CMKLR1/Chem R23 which is its principal receptor.[18] McCarthy et al. documented that Chemerin by its ability for chemotactic recruitment of macrophages and dendritic cells expressing CMKLR1, as well as by its ability to promote cholesterol uptake and foam cell formation, may play a central role in atherosclerosis.[19] With this information in the backdrop, many studies were carried out to assess the association of Chemerin with CADs and to evaluate whether Chemerin like hs-CRP could be used as a surrogate marker for them. Most of them showed Chemerin levels to be elevated in CAD patients, more so if they were suffering from metabolic syndrome/Type 2 DM simultaneously.[20],[21],[22],[23],[24],[25],[26]

In India, Cardiovascular diseases and DM constitute a major social and economic burden and are the leading causes of mortality. ACSs account for 80% of the deaths associated with these.[27] Researches studying the role of Chemerin in these diseases are lacking in India.

Hence, this study was undertaken with the aim to assess role of serum Chemerin in patients of ACS and draw a comparison among cardiodiabetics versus nondiabetics. We found that serum Chemerin levels were higher in patients of ACS as compared to controls. We also observed that Chemerin levels were higher in cardiodiabetics compared to the nondiabetics. On similar lines, Kadoglou et al., and Hamdy et al., in their respective studies observed that Chemerin levels are higher in AMI patients with DM compared to AMI nondiabetics.[12],[13] Salama et al., and Elnajjar et al., also reported Chemerin levels to be significantly higher in CAD patients with DM compared to those without DM.[28],[29]

hs CRP, CK-MB, and Trop-I were observed to be higher in patients of ACS with DM than the ACS-NDM ones. The serum Chemerin levels showed a positive correlation with all the three parameters, though it was found to be significant only for hs CRP and Trop-I, not for CK-MB. Ateş et al. who investigated plasma Chemerin levels in ST elevated myocardial infarction patients reported its significant positive correlation with peak CK-MB levels and inferred that Chemerin is a novel prognostic tool for AMI patients.[30] Recently, Zhou et al. conducted a study to evaluate the prognostic value of serum Chemerin in patients with chronic heart failure and documented that Chemerin was highly useful in predicting major adverse cardiac events in these patients.[15]

In the present era of targeted and personalized therapy, the inclusion of Chemerin as a diagnostic marker in CADs may prove to be of paramount importance because of the option of availing anti chemerin drugs which currently in trial phase target its main receptor (anti-Chem R 23). This may help to radically redefine the management of such patients and avert catastrophic consequences.

The present study showed that Chemerin is a new biomarker which is significantly elevated in acute cardiovascular events and it shows a positive correlation with all the other three biomarkers, i.e., hs CRP, CK-MB and Trop-I. It also states that Cardio diabetics fare worse with regards to all the above-mentioned parameters.

Regarding the limitations, one limitation was the small sample size being a single-center-based study. Other limitation was the study design which was cross-sectional, thus predictive/prognostic significance of Chemerin could not be assessed.

We recommend multicenter longitudinal studies to be undertaken in future to understand the full potential of Chemerin as a diagnostic/prognostic/predictive biomarker of acute cardiovascular events. Furthermore, its role in various complications of diabetes warrants thorough research.


  Conclusion Top


This is the first study done in India done to assess the circulating Chemerin levels in patients of ACS. Chemerin levels were found to be high in patients of ACS. In addition, Chemerin showed a positive correlation with hs CRP, CK-MB, and Trop-I. All these four biomarkers were significantly more deranged in cardiodiabetics. Hence, we conclude that Chemerin is a novel biomarker of ACS with the possible potential benefit of being used as a targeted therapy, especially in cardiodiabetics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Yan Q, Zhang Y, Hong J, Gu W, Dai M, Shi J, et al. The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine 2012;41:281-8.  Back to cited text no. 1
    
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Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, et al. Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Lett 2008;582:573-8.  Back to cited text no. 2
    
3.
Nagpal S, Patel S, Jacobe H, DiSepio D, Ghosn C, Malhotra M, et al. Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol 1997;109:91-5.  Back to cited text no. 3
    
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Zabel BA, Zuniga L, Ohyama T, Allen SJ, Cichy J, Handel TM, et al. Chemoattractants, extracellular proteases, and the integrated host defense response. Exp Hematol 2006;34:1021-32.  Back to cited text no. 4
    
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Guillabert A, Wittamer V, Bondue B, Godot V, Imbault V, Parmentier M, et al. Role of neutrophil proteinase 3 and mast cell chymase in chemerin proteolytic regulation. J Leukoc Biol 2008;84:1530-8.  Back to cited text no. 6
    
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Lin X, Tang X, Jiang Q, Liu Q, Lin Z, Lin J, et al. Elevated serum chemerin levels are associated with the presence of coronary artery disease in patients with type 2 diabetes. Clin Lab 2012;58:539-44.  Back to cited text no. 10
    
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Lu B, Zhao M, Jiang W, Ma J, Yang C, Shao J, et al. Independent association of circulating level of chemerin with functional and early morphological vascular changes in newly diagnosed type 2 diabetic patients. Medicine (Baltimore) 2015;94:e1990.  Back to cited text no. 11
    
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Kadoglou NP, Tahmatzidis DK, Giannakoulas C, Kapelouzou A, Gkontopoulos A, Parissis J, et al. Serum levels of novel adipokines, omentin-1 and chemerin, in patients with acute myocardial infarction: Kozani study. J Cardiovasc Med (Hagerstown) 2015;16:341-6.  Back to cited text no. 12
    
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Hamdy H, Ghoneim W, Abdelmonem H, Ali I, Emam M. Chemerin novel biomarker as a prognostic factor for cardiovascular complications in type 2 diabetic patients. Egypt J Hosp Med 2016;65:491-97.  Back to cited text no. 13
    
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Ji Q, Lin Y, Liang Z, Yu K, Liu Y, Fang Z, et al. Chemerin is a novel biomarker of acute coronary syndrome but not of stable angina pectoris. Cardiovasc Diabetol 2014;13:145-53  Back to cited text no. 14
    
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Zhou X, Tao Y, Chen Y, Xu W, Qian Z, Lu X. Serum Chemerin as a Novel Prognostic Indicator in Chronic Heart Failure. J Am Heart Assoc 2019;8:e012091.  Back to cited text no. 15
    
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Zhou Q, Fu Y, Hu L, Li Q, Jin M, Jiang E. Relationship of circulating chemerin and omentin levels with Th 17 and Th 9 cell immune responses in patients with asthma. J Asthma 2018;55:579-87.  Back to cited text no. 17
    
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Kaur J, Adya R, Tan BK, Chen J, Randeva HS. Identification of chemerin receptor (ChemR23) in human endothelial cells: Chemerin-induced endothelial angiogenesis. Biochem Biophys Res Commun 2010;391:1762-8.  Back to cited text no. 18
    
19.
McCarthy TC, Zúñiga LA, Zabel BA, Butcher EC, Sinal CJ. The novel adipokine Chemerin significantly increases cholesterol uptake in human macrophages. Fed Am Soc Exp Biol J 2008;22:948-58.  Back to cited text no. 19
    
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Dong B, Ji W, Zhang Y. Elevated serum chemerin levels are associated with the presence of coronary artery disease in patients with metabolic syndrome. Intern Med 2011;50:1093-7.  Back to cited text no. 22
    
23.
Yan Q, Zhang Y, Hong J, Gu W, Dai M, Shi J, et al. The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine 2012;41:281-8.  Back to cited text no. 23
    
24.
El-Mesallamy HO, El-Derany MO, Hamdy NM. Serum omentin-1 and chemerin levels are interrelated in patients with Type 2 diabetes mellitus with or without ischaemic heart disease. Diabet Med 2011;28:1194-200.  Back to cited text no. 24
    
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Hu W, Feng P. Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients. Diabetes Res Clin Pract 2011;91:159-63.  Back to cited text no. 25
    
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Yoo HJ, Choi HY, Yang SJ, Kim HY, Seo JA, Kim SG, et al. Circulating chemerin level is independently correlated with arterial stiffness. J Atheroscler Thromb 2012;19:59-66.  Back to cited text no. 26
    
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Salama FE, Anass QA, Abdelrahman AA, Saeed EB. Chemerin: A biomarker for cardiovascular disease in diabetic chronic kidney disease patients. Saudi J Kidney Dis Transpl 2016;27:977-84  Back to cited text no. 28
    
29.
Elnajjar MM, Dawood AA, Soliman MA, Khalil GI, Elzorkany KMA, Aglan MFM. Serum chemerin and its association with coronary heart disease in diabetic and nondiabetic patients. Menoufia Med J 2017;31:474-80.  Back to cited text no. 29
    
30.
Ateş AH, Arslan U, Aksakal A, Yanık A, Özdemir M, Kul S. Plasma chemerin levels are increased in ST elevation myocardial infarction patients with high thrombus burden. Cardiol Res Pract 2018;2018:5812704.  Back to cited text no. 30
    



 
 
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