Abstract
Atherosclerosis causes significant morbidity and mortality. Carotid intima media thickness (IMT) predicts future ischaemic strok e incidence. Matrix metalloproteinases (MMPs) play a considerable role in atherosclerosis and hold therapeutic promise as well. To investigate the relationship between serum level of matrix metalloproteinase-9 (MMP-9) and common carotid artery intima media thickness (CCA-IMT) in patients with ischaemic stroke and asymptomatic subjects. Thirty patients with a previous ischaemic stroke and 30 asymptomatic volunteers were recruited. Assessment of vascular risk factors, serum level of MMP-9 and CCA-IMT on both sides was performed. The IMT of both CCAs correlated positively with the serum MMP-9 level in asymptomatic subjects (p = 0.000), even after adjustment for other risk factors. In the patients group, this positive correlation was significant for the right but not for the left CCA (right CCA: p = 0.023, left CCA: p = 0.0284). Fasting blood sugar correlated positively with serum levels of MMP-9 in asymptomatic subjects (p = 0.005) but did not correlate positively in patients. There was no significant correlation between MMP-9 and age or other investigated laboratory risk factors in either the patient or asymptomatic groups. MMP-9 is positively correlated with CCA-IMT both in stroke patients and asymptomatic subjects. This may indicate that MMP-9 is a possible therapeutic target for stroke prevention.
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References
Baker AH, Zaltsman AB, George SJ, Newby AC (1998) Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis. J Clin Invest 101:1478–1487
Bendeck MP, Irvin C, Reidy MA (1996) Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ Res 78:38–43
Bendeck MP, Zempo N, Clowes AW, Galardy RE, Reidy MA (1994) Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ Res 75:539–545
Brew K, Dinakarpandian D, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Acta 1477:267–283
Chau KY, Sivaprasad S, Patel N, Donaldson TA, Luthert PJ, Chong NV (2007) Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in age-related macular degeneration. Eye (Lond) 21:1511–1515
Choudhary S, Higgins CL, Chen IY, Reardon M, Lawrie G, Vick GW, Karmonik C, Via DP, Morrisett JD (2006) Quantitation and localization of matrix metalloproteinases and their inhibitors in human carotid endarterectomy tissues. Arterioscler Thromb Vasc Biol 26:2351–2358
Clark AW, Krekoski CA, Bou SS, Chapman KR, Edwards DR (1997) Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia. Neurosci Lett 238:53–56
Eldrup N, Grønholdt M-LM, Sillesen H, Nordestgaard BG (2006) Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular death in patients with carotid stenosis. Circulation 114:1847–1854
Forough R, Koyama N, Hasenstab D, Lea H, Clowes M, Nikkari ST, Clowes AW (1996) Overexpression of tissue inhibitor of matrix metalloproteinase-1 inhibits vascular smooth muscle cell functions in vitro and in vivo. Circ Res 79:812–820
Forough R, Lea H, Starcher B, Allaire E, Clowes M, Hasenstab D, Clowes AW (1998) Metalloproteinase blockade by local overexpression of TIMP-1 increases elastin accumulation in rat carotid artery intima. Arterioscler Thromb Vasc Biol 18:803–807
Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90:251–262
Galis ZS, Sukhova GK, Lark MW, Libby P (1994) Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 94:2493–2503
Godin D, Ivan E, Johnson C, Magid R, Galis ZS (2000) Remodeling of carotid artery is associated with increased expression of matrix metalloproteinases in mouse blood flow cessation model. Circulation 102:2861–2866
Higashikata T, Yamagishi M, Higashi T et al (2006) Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption: results of quantitative tissue analysis using real-time RT-PCR method. Atherosclerosis 185:165–172
Johnson JL, Jackson CL, Angelini GD, George SJ (1998) Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 18:1707–1715
Jormsjö S, Ye S, Moritz J, Walter DH, Dimmeler S, Zeiher AM, Henney A, Hamsten A, Eriksson P (2000) Allele-specific regulation of matrix metalloproteinase-12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease. Circ Res 86:998–1003
Kim S-J, Chung Y-K, Chung T-W, Kim J-R, Moon S-K, Kim C-H, Park Y-G (2009) Regulation of matrix metalloproteinase-9 expression between gingival fibroblast cells from old and young rats. Biochem Biophys Res Commun 378:152–156
Kornowski R, Mintz GS, Lansky AJ, Hong MK, Kent KM, Pichard AD, Satler LF, Popma JJ, Bucher TA, Leon MB (1998) Paradoxic decreases in atherosclerotic plaque mass in insulin-treated diabetic patients. Am J Cardiol 81:1298–1304
Lutgens E, Lutgens SPM, Faber BCG et al (2006) Disruption of the Cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation 113:98–107
Machado L, Kozak A, Ergul A, Hess D, Borlongan C, Fagan S (2006) Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci 7(1):56
Mackinnon AD, Jerrard-Dunne P, Sitzer M, Buehler A, Von Kegler S, Markus HS (2004) Rates and determinants of site-specific progression of carotid artery intima-media thickness: the carotid atherosclerosis progression study. Stroke 35:2150–2154
Mason DP, Kenagy RD, Hasenstab D, Bowen-Pope DF, Seifert RA, Coats S, Hawkins SM, Clowes AW (1999) Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery. Circ Res 85:1179–1185
Matrisian LM (1990) Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121–125
Noji Y, Kajinami K, Kawashiri MA et al (2001) Circulating matrix metalloproteinases and their inhibitors in premature coronary atherosclerosis. Clin Chem Lab Med 39:380–384
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 340:14–22
Olson FJ, Schmidt C, Gummesson A, Sigurdardottir V, Hulthe J, Wiklund O, Fagerberg B (2008) Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis. J Intern Med 263:626–635
Romero JR, Vasan RS, Beiser AS, Polak JF, Benjamin EJ, Wolf PA, Seshadri S (2008) Association of carotid artery atherosclerosis with circulating biomarkers of extracellular matrix remodeling: the Framingham offspring study. J Stroke Cerebrovasc Dis 17:412–417
Rybakowski JK (2009) Matrix metalloproteinase-9 (MMP9)-a mediating enzyme in cardiovascular disease, cancer, and neuropsychiatric disorders. Cardiovasc Psychiatry Neurol 2009:904836
Sapienza P, Di Marzo L, Borrelli V, Sterpetti AV, Mingoli A, Cresti S, Cavallaro A (2005) Metalloproteinases and their inhibitors are markers of plaque instability. Surgery 137:355–363
Somiari SB, Somiari RI, Heckman CM, Olsen CH, Jordan RM, Russell SJ, Shriver CD (2006) Circulating MMP2 and MMP9 in breast cancer—potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer 119:1403–1411
Southgate KM, Davies M, Booth RF, Newby AC (1992) Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation. Biochem J 288(Pt 1):93–99
Tan C, Liu Y, Li W, Deng F, Liu X, Wang X, Gui Y, Qin L, Hu C, Chen L (2014) Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis, based on measurements of plaque and intima-media thickness. Atherosclerosis 232:199–203
Tauth J, Pinnow E, Sullebarger JT, Basta L, Gursoy S, Lindsay J, Matar F (1997) Predictors of coronary arterial remodeling patterns in patients with myocardial ischemia. Am J Cardiol 80:1352–1355
Tayebjee MH, Tan KT, MacFadyen RJ, Lip GYH (2005) Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: Relationship to disease severity. J Intern Med 257:110–116
Wang Y, Deng X-L, Xiao X-H, Yuan B-X (2007) A non-steroidal anti-inflammatory agent provides significant protection during focal ischemic stroke with decreased expression of matrix metalloproteinases. Curr Neurovasc Res 4:176–183
Zhang Y, Stewart KG, Davidge ST (2000) Estrogen replacement reduces age-associated remodeling in rat mesenteric arteries. Hypertension 36:970–974
Zhang B, Ye S, Herrmann SM et al (1999) Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 99:1788–1794
Zhou S, Feely J, Spiers JP, Mahmud A (2007) Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension. J Hum Hypertens 21:861–867
Zureik M, Beaudeux J-L, Courbon D, Bénétos A, Ducimetière P (2005) Serum tissue inhibitors of metalloproteinases 1 (TIMP-1) and carotid atherosclerosis and aortic arterial stiffness. J Hypertens 23:2263–2268
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This study was done using Cairo University facilities. Authors did not receive any grant or fund to accomplish this work.
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Abdelnaseer, M., Elfayomi, N., Esmail, E.H. et al. Relationship between matrix metalloproteinase-9 and common carotid artery intima media thickness. Neurol Sci 37, 117–122 (2016). https://doi.org/10.1007/s10072-015-2358-z
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DOI: https://doi.org/10.1007/s10072-015-2358-z