Serum Matrix Metalloproteinase 3 and Tissue Inhibitor Metalloproteinase 1 in Vascular Dementia: A Comparative Study

Mohammed Zain Abdelwadoud Hussein

Ain Shams University Hospital, Cairo, Egypt.

DOI: 10.4236/aar.2015.45016                

Abstract

Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups; vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.

Keywords

Multiinfarct Dementia, Matrix Metalloproteinase 3, Tissue Inhibitor Me, Talloproteinase 1, Vascular Dementia, Vascular Dementia of Subcortical Type

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	http://www.alz.org/dementia/vascular-dementia-symptoms.asp
[2]	Pavlovic, A., Pavlovic, D., Aleksic, V. and Sternic, N. (2013) Vascular Dementia: Facts and Controversies. Srp Arch CelokLek, 141, 247-255.
[3]	Hebert, R. and Brayne, C. (1995) Epidemiology of Vascular Dementia. Neuroepidemiology, 14, 240. http://dx.doi.org/10.1159/000109800
[4]	Wright, C.B. (2015) Etiology, Clinical Manifestations and Diagnosis of Vascular Dementia (on Line). www.uptodate.com/contents/etiology-clinical-manifestations-anddiagnosis-of-vasculardementia?Source=search_result&search+vascular+dementia&selected Title = 1~44
[5]	Gorelick, P.B., Scuteri, A., Black, S.E., Decarli, C., Greenberg, S.M., Iadecola, C., et al. (2011) Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke, 42, 2672-2713. http://dx.doi.org/10.1161/STR.0b013e3182299496
[6]	Benisty, S. (2013) Current Concepts in Vascular Dementia. Geriatr Psychol Neuropsychiatr Vieil, 11, 171-180.
[7]	Hachinski, V., Iadecola, C., Petersen, R.C., Breteler, M.M., Nyenhuis, D.L., Black, S.E., et al. (2006) National Institute of Neurological Disorders and Stroke—Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards. Stroke, 37, 2220-2241. http://dx.doi.org/10.1161/01.STR.0000237236.88823.47
[8]	Caplan, L.R. (1995) Binswanger’s Disease—Revisited. Neurology, 45, 626-633. http://dx.doi.org/10.1212/WNL.45.4.626
[9]	Olszewski, J. (1962) Subcortical Arteriosclerotic Encephalopathy. Review of the Literature on the So-Called Binswanger’s Disease and Presentation of Two Cases. World Neurology, 3, 359-375.
[10]	Malemud, C.J. (2006) Matrix Metalloproteinases (MMPs) in Health and Disease: An Overview. Frontiers in Bioscience, 11, 1696-1701. (Review).
[11]	Mroczko, B., Groblewska, M. and Barcikowska, M. (2013) The Role of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in the Pathophysiology of Neurodegeneration: A Literature Study. Journal of Alzheimer’s Disease, 37, 273-283.
[12]	Rosenberg, G.A., Navratil, M., Barone, F. and Feuerstein, G. (1996) Proteolytic Cascade Enzymes Increase in Focal Cerebral Ischemia in Rat. Journal of Cerebral Blood Flow & Metabolism, 55, 300-309
[13]	Stomrud, E., Björkqvist, M., Janciauskiene, S., Minthon, L. and Hansson, O. (2010) Alterations of Matrix Metalloproteinases in the Healthy Elderly with Increased Risk of Prodromal Alzheimer’s Disease. Alzheimer’s Research & Therapy, 2, 20. http://dx.doi.org/10.1186/alzrt44
[14]	Helbecque, N., Cottel, D., Hermant, X. and Amouyel, P. (2007) Impact of the Matrix Metalloproteinase MMP-3 on Dementia. Neurobiology of Aging, 28, 1215-1220. http://dx.doi.org/10.1016/j.neurobiolaging.2006.05.030
[15]	Saarela, M.S., Lehtimäki, T., Rinne, J.O., Hervonen, A., Jylhä, M., Röyttä, M., et al. (2004) Interaction between Matrix Metalloproteinase 3 and the Epsilon 4 Allele of Apolipoprotein E Increases the Risk of Alzheimer’s Disease in Finns. Neuroscience Letters, 367, 336-339. http://dx.doi.org/10.1016/j.neulet.2004.06.027
[16]	Maeda, A. and Sobel, R.A. (1996) Matrix Metalloproteinases in the Normal Human Central Nervous System, Microglial Nodules, and Multiple Sclerosis Lesions. Journal of Neuropathology and Experimental Neurology, 55, 300-309. http://dx.doi.org/10.1097/00005072-199603000-00005
[17]	Clark, A.W., Krekoski, C.A., Bou, S.S., Chapman, K.R. and Edwards, D.R. (1997) Increased Gelatinase A (MMP-2) and Gelatinase B (MMP-9) Activities in Human Brain after Focal Ischemia. Neuroscience Letters, 238, 53-56. http://dx.doi.org/10.1016/S0304-3940(97)00859-8
[18]	Anthony, D.C., Ferguson, B., Matyzak, M.K., Miller, K.M., Esiri, M.M. and Perry, V.H. (1997) Differential Matrix Metalloproteinase Expression in Cases of Multiple Sclerosis and Stroke. Neuropathology and Applied Neurobiology, 23, 406-415. http://dx.doi.org/10.1111/j.1365-2990.1997.tb01315.x
[19]	Rosenberg, G.A., Sullivan, N. and Esiri, M.M. (2001) White Matter Damage Is Associated with Matrix Metalloproteinases in Vascular Dementia. Stroke, 32, 1162-1168. http://dx.doi.org/10.1161/01.STR.32.5.1162
[20]	Roman, G.C., Tatemichi, T.K., Erkinjuntti, T., Cummings, J.L., Masdeu, J.C., Garcia, J.H., Amaducci, L., Orgogozo, J.M., Brun, A., Hofman, A., et al. (1993) Vascular Dementia: Diagnostic Criteria for Research Studies. Report of the NINDS-AIREN International Workshop. Neurology, 43, 250-260. http://dx.doi.org/10.1212/WNL.43.2.250
[21]	Boster Biological Technology Co., Ltd. (2014) http://www.bosterbio.com/human-timp-1-picokine-elisa-kitek0520.html
[22]	Boster Biological Technology Co., Ltd. (2014) http://www.bosterbio.com/human-mmp-3-picokine-elisa-kitek0461.html
[23]	Chakraborti, S., Mandal, M., Das, S., Mandal, A. and Chakraborti, T. (2003) Regulation of Matrix Metalloproteinases: An Overview. Molecular and Cellular Biochemistry, 253, 269-285. http://dx.doi.org/10.1023/A:1026028303196
[24]	Rosenberg, G.A., Cunningham, L.A., Wallace, J., Alexander, S., Estrada, E.Y., Grossetete, M., et al. (2001) Immunohistochemistry of Matrix Metalloproteinases in Reperfusion Injury to Rat Brain: Activation of MMP-9 Linked to Stromelysin-1 and Microglia in Cell Cultures. Brain Research, 893, 104-112. http://dx.doi.org/10.1016/S0006-8993(00)03294-7
[25]	Lorenzl, S., Buerger, K., Hampel, H. and Beal, M.F. (2008) Profiles of Matrix Metalloproteinases and Their Inhibitors in Plasma of Patients with Dementia. International Psychogeriatrics, 20, 67-76. http://dx.doi.org/10.1017/s1041610207005790
[26]	Stetler-Stevenson, W.G. (2008) The Tumor Microenvironment: Regulation by MMP-Independent Effects of Tissue Inhibitor of Metalloproteinases-2. Cancer and Metastasis Reviews, 27, 57-66. http://dx.doi.org/10.1007/s10555-007-9105-8
[27]	Lovelock, J.D., Baker, A.H., Gao, F., Dong, J.F., Bergeron, A.L., McPheat, W., et al. (2005) Heterogeneous Effects of Tissue Inhibitors of Matrix Metalloproteinases on Cardiac Fibroblasts. AJP: Heart and Circulatory Physiology, 288, H461-H468. http://dx.doi.org/10.1152/ajpheart.00402.2004
[28]	Roycik, M.D., Myers, J.S., Newcomer, R.G. and Sang, Q.X. (2013) Matrix Metalloproteinase Inhibition in Atherosclerosis and Stroke. Current Molecular Medicine, 13, 1299-1313. http://dx.doi.org/10.2174/15665240113139990067