Association between Increased Matrix Metalloproteinase-9 (MMP-9) Levels with Hyperglycaemia Incidence in Acute Ischemic Stroke Patients

Ismail Setyopranoto; Rusdy Ghazali Malueka; Andre Stefanus Panggabean; I Putu Eka Widyadharma; Ahmad Hamim Sadewa; Rusdi Lamsudin; Samekto Wibowo

doi:10.3889/oamjms.2018.459

Authors

Ismail Setyopranoto Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia https://orcid.org/0000-0003-4768-7113
Rusdy Ghazali Malueka Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia https://orcid.org/0000-0001-6835-0638
Andre Stefanus Panggabean Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia https://orcid.org/0000-0002-0459-3339
I Putu Eka Widyadharma Department of Neurology, Faculty of Medicine, Udayana University and Sanglah General Hospital, Bali, Indonesia https://orcid.org/0000-0002-4554-0348
Ahmad Hamim Sadewa Department of Biochemistry, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia https://orcid.org/0000-0002-3514-6646
Rusdi Lamsudin Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia
Samekto Wibowo Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada and Dr Sardjito General Hospital, Yogyakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2018.459

Keywords:

Hyperglycemia, Matrix metalloproteinase-9 (MMP-9), Acute ischemic stroke

Abstract

BACKGROUND: Hyperglycemia is common in acute stroke patients. Hyperglycemia can induce the production of reactive oxygen species, causing increased activity of matrix metalloproteinase-9 (MMP-9).

AIM: This study aimed to determine an association between the increased levels of MMP-9 and the incidence of hyperglycemia in acute ischemic stroke patients.

METHODS: This is a case-control study. Acute ischemic stroke patients admitted to the Stroke Unit of a reference hospital in Yogyakarta, Indonesia was divided into the hyperglycemic and non-hyperglycemic group. Demographic and clinical characteristics of each subject were recorded, and blood levels of MMP-9 were measured. Seventy-one patients were recruited, 40 subjects in the hyperglycemic group and 31 subjects in the non-hyperglycemic group.

RESULTS: The median levels of blood MMP-9 level in the hyperglycemic and non-hyperglycemic group were 974.37 and 748.48 ng/mL, respectively, and the difference was statistically not significant (95% CI, 191.24-2849.53; p = 0.07). When the calculated cut-off point of 600.99 ng/mL was used, the proportion of patients with higher MMP-9 levels was significantly more in the hyperglycemic group compared with the ones in the non-hyperglycemic group (82.5% and 54.8%, respectively; OR = 3.88; p = 0.011).

CONCLUSION: We concluded that the proportion of patients with MMP-9 level >600.99 ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

A. D. Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012; 35:S64-71. https://doi.org/10.2337/dc12-s064 PMid:22187472 PMCid:PMC3632174

Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, Fineberg SE, Tierney WR. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurol. 2002; 59:67-71. https://doi.org/10.1212/WNL.59.1.67

Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke. 2006; 37:267-73. https://doi.org/10.1161/01.STR.0000195175.29487.30 PMid:16306459

Bevers MB, Vaishnav NH, Pham L, Battey TW, Kimberly WT. Hyperglycemia is associated with more severe cytotoxic injury after stroke. J Cereb Blood Flow Metab. 2016; 37:2577-83. https://doi.org/10.1177/0271678X16671730 PMid:27671250 PMCid:PMC5531353

Uemura S, Matsushita H, Li W, Glassford AJ, Asagami T, Lee KH, Harrison DG, Tsao PS. Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circ Res. 2001; 88:1291-8. https://doi.org/10.1161/hh1201.092042 PMid:11420306

Aljada A, Ghanim H, Mohanty P, Syed T, Bandyopadhyay A, Dandona P. Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations. Am J Clin Nutr. 2004; 80:51-7. https://doi.org/10.1093/ajcn/80.1.51 PMid:15213027

Zhao BQ, Tejima E, Lo EH. Neurovascular proteases in brain injury, hemorrhage and remodeling after stroke. Stroke. 2007; 38:748-52. https://doi.org/10.1161/01.STR.0000253500.32979.d1 PMid:17261731

Montaner J, Alvarez-SabÃn J, Molina C, AnglÃ©s A, Abilleira S, Arenillas J, GonzÃ¡lez MA, Monasterio J. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke. 2001; 32:1759-66. https://doi.org/10.1161/01.STR.32.8.1759 PMid:11486102

Abdelnaseer M, Elfayomi N, Hassan E, Kamal M, Hamdy A, Elsawy E. Serum matrix metalloproteinase-9 in acute ischemic stroke and its relation to stroke severity. Egypt J Neurol Psychiatry Neurosurg. 2015; 52:274-8. https://doi.org/10.4103/1110-1083.170661

Barr TL, Latour LL, Lee KY, Schaewe TJ, Luby M, Chang GS, El-Zammar Z, Alam S, Hallenbeck JM, Kidwell CS, Warach S. Blood brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. Stroke. 2010; 41:123-8. https://doi.org/10.1161/STROKEAHA.109.570515 PMid:20035078 PMCid:PMC2827673

Hao Y, Tian S, Sun M, Zhu Y, Nie Z, Yang, S. Association between matrix metalloproteinase gene polymorphisms and development of ischemic stroke. Int J Clin Exp Pathol. 2015; 11647-52. PMid:26617904 PMCid:PMC4637720

Buraczynska K, Kurzepa J, Ksiazek A, Buraczynska M, Rejdak K. Matrix metalloproteinase-9 (MMP-9) gene polymorphism in stroke patients. Neuromolecular Med. 2015; 17:385-90. https://doi.org/10.1007/s12017-015-8367-5 PMid:26330106 PMCid:PMC4643105

Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science. 2002; 297:1186-90. https://doi.org/10.1126/science.1073634 PMid:12183632

Chaturvedi M, Kaczmarek L. MMP-9 inhibition: a therapeutic strategy in ischemic stroke. Mol Neurobiol. 2014; 49:563-73. https://doi.org/10.1007/s12035-013-8538-z PMid:24026771 PMCid:PMC3918117

PÃ¶llÃ¤nen PJ, Karhunen PJ, Mikkelsson J, Laippala P, Perola M, PenttilÃ¤ A, Mattila KM, Koivula T, LehtimÃ¤ki T. Coronary artery complicated lesion area is related to functional polymorphism of matrix metalloproteinase 9 gene: an autopsy study. Arterioscler Thromb Vasc Biol. 2001; 21:1446-1450. https://doi.org/10.1161/hq0901.095545 PMid:11557670

Lamsudin R. Reliability of Gadjah Mada Stroke Scale (GMSS) in stroke patients. In: PERDOSSI. Buku Abstrak Musyawarah Kerja dan Pertemuan Ilmiah Tahunan Perdossi, PERDOSSI: Malang, Indonesia, 1998.

Kamada H, Yu F, Nito C, Chan PH. Influence of hyperglycemia on oxidative stress and MMP-9 activation after focal cerebral ischemia/reperfusion in ats: relationship to blood-brain barrier dysfunction. Stroke. 2007; 38:1044-9. https://doi.org/10.1161/01.STR.0000258041.75739.cb PMid:17272778 PMCid:PMC1828129

Sapojnikova N, Kartvelishvili T, Asatiani N, Zinkevich V, Kalandadze I, Gugutsidze D, Shakarishvili R, Tsiskaridze A. Correlation between MMP-9 and extracellular cytokine HMGB1 in prediction of human ischemic stroke outcome. Biochim Biophys Acta. 2014; 1842:1379-84. https://doi.org/10.1016/j.bbadis.2014.04.031 PMid:24815357

Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, Wang X, Rosenberg GA, Lo EH, Moskowitz MA. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest. 2004; 113:1447-55. https://doi.org/10.1172/JCI200421227 PMid:15146242 PMCid:PMC406541

Hsieh HL, Chi PL, Lin CC, Yang CC, Yang CM. Up-regulation of ROS-dependent matrix metalloproteinase-9 from high-glucose-challenged astrocytes contributes to the neuronal apoptosis. Mol Neurobiol. 2014; 50:520-33. https://doi.org/10.1007/s12035-013-8628-y PMid:24395134

Tsai WC, Liang FC, Cheng JW, Lin LP, Chang SC, Chen HH, Pang JH. High glucose concentration up-regulates the expression of matrix metalloproteinase-9 and -13 in tendon cells. BMC Musculoskelet Disord. 2013; 14:255. https://doi.org/10.1186/1471-2474-14-255 PMid:23981230 PMCid:PMC3765930

Sachwani GR, Jaehne AK, Jayaprakash N, Kuzich M, Onkoba V, Blyden D, Rivers EP. The association between blood glucose levels and matrix-metalloproteinase-9 in early severe sepsis and septic shock. J Inflamm. 2016; 13:1-8. https://doi.org/10.1186/s12950-016-0122-7 PMid:27110221 PMCid:PMC4840979

Planas AM, SolÃ© S, Justicia C. Expression and activation of matrix metalloproteinase-2 and -9 in rat brain after transient focal cerebral ischemia. Neurobiol Dis. 2001; 8:834-46. https://doi.org/10.1006/nbdi.2001.0435 PMid:11592852

Turner RJ, Sharp FR. Implications of MMP9 for blood brain barrier disruption and hemorrhagic transformation following ischemic stroke. Front Cell Neurosci. 2016; 10:1-13. https://doi.org/10.3389/fncel.2016.00056 PMid:26973468 PMCid:PMC4777722

Park KP, Rosell A, Foerch C, Xing C, Kim WJ, Lee S, Opdenakker G, Furie KL, Lo EH. Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats. Stroke. 2009; 40:2836-42. https://doi.org/10.1161/STROKEAHA.109.554824 PMid:19556529 PMCid:PMC3712850

Demir R, Ulvi H, Ozel L, Ã–zdemir G, GÃ¼zelcik M, AygÃ¼l R. Relationship between plasma metalloproteinase-9 levels and volume and severity of infarct in patients with acute ischemic stroke. Acta Neurol Belg. 2012; 112:351-6. https://doi.org/10.1007/s13760-012-0067-4 PMid:22581515

Abdelnaseer MM, Elfauomy NM, Esmail EH, Kamal MM, Elsawy EH. Matrix metalloproteinase-9 and recovery of acute ischemic stroke. J Stroke Cerebrovasc Dis. 2017; 26:733-40. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.09.043 PMid:28063771

Zhong C, Yang J, Xu T, Xu T, Peng Y, Wang A, Wang J, Peng H, Li Q, Ju Z, Geng D, Zhang Y, He J; CATIS Investigators. Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke. Neurol. 2017; 89:805-12. https://doi.org/10.1212/WNL.0000000000004257 PMid:28747453 PMCid:PMC5580861

Elgebaly MM, Ogbi S, Li W, Mezzetti EM, Prakash R, Johnson MH, Bruno A, Fagan SC, Ergul A. Neurovascular injury in acute hyperglycemia and diabetes: a comparative analysis in experimental stroke. Transl Stroke Res. 2011; 2:391-8. https://doi.org/10.1007/s12975-011-0083-3 PMid:21909340 PMCid:PMC3169178

Yu X, Xu X, Jackson A, Sun J, Huang P, Mao Y, Chen Z, Lou M, Jiang Q, Zhang M. Blood brain barrier disruption in diabetic stroke related to unfavorable outcome. Cerebrovasc Dis. 2016; 42:49-56. https://doi.org/10.1159/000444809 PMid:26986824