Chitotriosidase Enzyme Activity and miRNA-146a expression and their value as potential Biomarkers of subclinical Atherosclerosis in type 2 Diabetes Mellitus

Authors

  • Hala Mourad Demerdash Clinical Pathology Department, Faculty of Pharmacy, Alexandria University Hospitals, Pharos University in Alexandria
  • Radwa Mohamed ElSharaby Faculty of Medicine Tanta University
  • Yasser Mohamed AblelRaouf Faculty of medicine, Tanta University

Keywords:

atherosclerosis, Chitotriosidase, MicroRNAs, Carotid Intimal-Medial Thickness

Abstract

Background:Type 2 diabetes T2DM is a common disease with increased mortality and morbidity due to vascular complications. Carotid Intimal-Medial Thickness (CIMT) is being used as a marker to assess subclinical atherosclerosis.MicroRNA (miR-146a) is a new discoveredbiomarker that regulates endothelial cell function and vascular inflammation, together with Chitotriosidase (CHIT1)enzyme being involved mainly in the immune and inflammatory responses.

This study aimed to investigate an assumed association between CHIT1 activity and miR-146a gene expression in type 2 diabetes patients for detection of endothelial dysfunction and subclinical atherosclerosis, in association with CIMT.

Material and methods: 30 control subjects (group I) and 100 patients diagnosed as T2DMclassified according to CIMT results; group II (38 patient) with CIMT value less than 0.7mm and group III (62patients) with CIMT value more than 0.7mm. Plasma CHIT1 activity was measured fluorometricallyand quantitative Real Time PCR (qPCR) for miR-146a. Routine laboratory parameters such as blood glucose, lipid profile, glycated hemoglobin were also measured.

Results revealedCHIT1activity was significant high(p < 0.001) in group II and III diabetic patients compared to group I, also it waspositively correlated with CIMT and other parameters as glycemic control, lipid profile, duration of disease and blood pressure. On the other hand, plasma miR-146a was significantly reduced (p < 0.001) in group III and was negatively correlated with CIMT and other parameters.

Conclusion:IncreasedCHIT1activity may be due to the associated changes in the relative gene expression of miRNA 146a in patients with increased CIMT above 1mm. Moreover, evaluation of microRNA 146a gene expression can be used as useful biomarker for detection of endothelial dysfunction and development of atherosclerosis in T2DM.

 

DOI: 10.21276/APALM.1346

References

1-Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J EndocrMetab 2016; 20:546-53.
2-Avogaro A, Albiero M, Menegazzo L, Kreutzenberg SD, Fadini GP. Endothelial dysfunction in diabetes—the role of reparatory mechanisms. Diabetes Care. 2011;34(2):285–90.
3- Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414:813–20.
4- Mudau M, Genis A, Lochner A, and Strijdom H. “Endothelial dysfunction: the early predictor of atherosclerosis”. Cardiovascular Journal of Africa. 2012; 23 (4): 222–231.
5- Di Rosa M, Malaguarnera G, De Gregorio C, Drago F, and Malaguarner L. Evaluation of CHI3L-1 and CHIT-1 Expression in Differentiated and Polarized Macrophages. Inflammation. 2013; 36(2):482-492.
6-Sheetz MJ, King GL.Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA2002; 288: 2579–2588.
7- Nomura K, Hamamoto Y, Takahara S, Kikuchi O, Honjo S, Ikeda H, Wada Y, Nabe K, Okumra R, Koshiyama H: Relationship between carotid intima media thickness and silent cerebral infarction in Japanese subjects with type 2 diabetes. Diabetes Care 2010;33(1):168–70.
8-Gayathri R, Chandni R, Udayabhaskaran V. Carotid artery intima media thickness in relation with atherosclerotic risk factors in patients with type 2 diabetes mellitus. J Assoc Physicians India 2012;60:20–4.
9- Butt MU, Zakaria M. Association of common carotid intimal medial thickness (CCA-IMT) with risk factors of atherosclerosis in patients with type 2 diabetes mellitus. J Pak Med Assoc. 2009;59(9):590-593.
10- Sibal L, Agarwal SC, Home PD. Carotid intima-media thickness as a surrogate marker of cardiovascular disease in diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2011; 4:23-34.
11- Kota S, Mahapatra G, and Mod K. Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke. Indian J of Endocrinol Metab.2013; 17(4): 716-722
12-Byrkjeland R, Stensæth K, Anderssen S, Njerve I, Arnesen H, Seljeflot I, and Solheim S. Effects of exercise training on carotid intima-media thickness in patients with type 2 diabetes and coronary artery disease. Influence of carotid plaques.Cardiovasc Diabetol. 2016; 15: 13.
13-Perumal K, Santha K, SethupathyS, Sethurajan S, Mahendran K, BalasubramaniyanS.Plasma homocysteine level and carotid intima–media thickness in type 2 diabetic patients. International J of Med Science and Public Health. 2015; 4 (10):1404-1408.
14-Di Rosa M and Malaguarnera L. Chitotriosidase: A New Inflammatory Marker in Diabetic Complications. Pathobiology 2016; 83:211–219.

15-Aguilera B, Ghauharali-van der Vlugt K, Helmond MT, Out JM, Donker-Koopman WE, Groener JE, et al: Transglycosidase activity of chitotriosidase: improved enzymatic assay for the human macrophage chitinase. J BiolChem 2003;278: 40911–40916.
16-Karadag B, Kucur M, Isman FK, Hacibekiroglu M, Vural VA: Serumchitotriosidase activity in patients with coronary artery disease. Circ J2008, 72:71-75.
17-Kitamoto S, Egashira K, Ichiki T, Han X, McCurdy S, Sakuda S, Sunagawa K, andBoisvert W. Chitinase Inhibition Promotes Atherosclerosis in Hyperlipidemic Mice. The American Journal of Pathology.2013; 183(1):313-325.
18- Artieda M, Cenarro A, Ganan A, Lukic A, Moreno E, Puzo J, et al: Serum chitotriosidase activity, a marker of activated macrophages, predicts new cardiovascular events independently of C-reactive protein. Cardiology 2007; 108: 297–306.
19- Boot RG, van Achterberg TA, van Aken BE, Renkema GH, Jacobs MJ, Aerts JM, de Vries CJ. Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. ArteriosclerThrombVascBiol 1999; 19: 687-94.
20- Di Rosa M TD, Saccone S, Distefano G, Basile MS, Di Raimondo F, MalaguarneraL.Chitotriosidase expression during monocyte-derived dendritic cells differentiation and maturation. Inflammation 2015;38:2082-2091.
21- Żurawska-Płaksej E, Ługowska A, Hetmańczyk K, Knapik-Kordecka M, PiwowaA. Neutrophils as a source of chitinases and chitinase-like proteins in type 2 diabetes.PLoS One 2015; 10:e0141730.

22-Ramanathan R, Kohli A, Ingaramo M, Jain A, Leng S, Punjabi P, Walston J and Fedarko N. Serum chitotriosidase, a putative marker of chronically activated macrophages, increases with normal aging. J Gerontol A Biol Sci Med Sci 2013; 68: 1303-10.
23-Siasos G, Kollia C, Tsigkou V, Basdra E, Lymperi M, Oikonomou E, Kokkou E, Korompelis P, Papavassiliou A. MicroRNAs: Novel diagnostic and prognostic biomarkers in atherosclerosis. Curr. Top. Med. Chem. 2013; 13:1503–1517.
24- Yang K, He Y, Wang Z, Lu L, Chen Q, Liu J, Sun Z, Shen W. MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4. FEBS Lett. 2011; 585:854–860.
25 -Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V. Impaired MIR-146a expression links subclinical inflammation and insulin resistance in type 2 diabetes. Mol. Cell Biochem. 2011;351:197–205.
26-Boldin M, Taganov K, Rao D, Yang L, Zhao J, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J, Sun G, Tay J, Linsley P, Baltimore D. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J. Exp. Med.2011;208:1189–1201.
27-Rong Y, Bao W, Shan Z, Liu J, Yu X, Xia S, Gao H, Wang X, Yao P, Hu F, Liu L.Increased MicroRNA-146a Levels in Plasma of Patients with Newly Diagnosed Type 2 Diabetes Mellitus. PLoS ONE.2013; 8(9): e73272.
28-O’Connell RM, Rao DS, Baltimore D. MicroRNA regulation of inflammatory responses. Annu Rev Immunol 2012 30:295–312.
29-Li K, Ching D, Luk FS, Raffai RL. Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-κB–driven inflammation and atherosclerosis. Circ Res. 2015;117: e1–e11.
30- Fernandez-Valverde SL, Taft RJ, Mattick JS. MicroRNAs in beta- cell biology, insulin resistance, diabetes and its complications. Diabetes. 2011; 60: 1825-1831.

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Published

07-07-2017

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1.
Demerdash HM, ElSharaby RM, AblelRaouf YM. Chitotriosidase Enzyme Activity and miRNA-146a expression and their value as potential Biomarkers of subclinical Atherosclerosis in type 2 Diabetes Mellitus. Ann of Pathol and Lab Med [Internet]. 2017 Jul. 7 [cited 2024 Dec. 26];4(3):A314-320. Available from: https://pacificejournals.com/journal/index.php/apalm/article/view/apalm1346

Issue

Vol. 4 No. 3 (2017)

Section

Original Article

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Copyright (c) 2017 Hala Mourad Demerdash, Radwa Mohamed ElSharaby, Yasser Mohamed AblelRaouf

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