Differences of Serum Ratio MMP-9/TIMP-1 in ST-Elevation Myocardial Infarction (STEMI) and Non ST-Elevation Acute Coronary Syndrome (NSTEACS)
Abstract
Background: Differences between the pathogenesis of ST-Elevation Myocardialinfarction (STEMI) and Non-ST Elevation Acute Coronary Syndrome
(NSTE-ACS) had yet unknown. Matrix metalloproteinase-9 (MMP-9) as the
matrix degradation enzyme secreted by inflammatory cells play a role in the
pathogenesis of plaque rupture. MMP-9 proteolytic activity is inhibited by
specific inhibitors of the Tissue Inhibitor of metalloproteinase-1 (TIMP-1).
MMP-9/TIMP-1 ratio describes the actual proteolytic activity of MMP-9.
This ratio may distinguish the pathogenesis of STEMI and NSTE-ACS.
Objective: To examine the difference serum level ratio MMP-9/TIMP-1 in
patients with STEMI and NSTE-ACS.
Methods and subjects: This is a cross-sectional study which recruits patients
consecutively with ACS admitted to ICCU of Dr. Sardjito General Hospital Yogyakarta
within 24 h onset. Acute infection, chronic inflammation, acute stroke,
kidney failure requiring renal replacement therapy, chronic heart failure, liver cirrhosis,
acute exacerbation of COPD and pneumonia, thromboembolic disease,
malignancy, pregnancy and the use of steroids and steroid anti-inflammatory
drugs are excluded. Serum levels of MMP-9 and TIMP-1 examined using the
method of sandwich enzyme-linked immunosorbent assay (ELISA).
Results: The total of 60 subjects with STEMI patients 31 (51.7%) and NSTEACS
29 (48.3%). Level of serum MMP-9/TIMP-1 ratio is significantly higher in
STEMI compared to NSTE-ACS (1.106 ± 0.065 vs. 1.046 ± 0.057, p <0.001).
MMP-9/TIMP-1 ratio in serum is an independent factor for STEMI (p = 0.003)
followed by blood sugar level (p = 0.013) and MMP-9 (p = 0.033). Interestingly,
patients with serum MMP-9/TIMP-1 ratio> 1.0639 has a prevalence risk
of 1.7 times having STEMI (p = 0.039; KI95% from 1.040 to 8.508). Levels of
serum MMP-9/TIMP-1 ratio significantly higher in STEMI compared to NSTEMI
group (p = 0.003) and in the STEMI and UAP group (0.026), but did not differ
significantly in NSTEMI and UAP group (p = 0.045).
Conclusion: High levels of serum MMP-9/TIMP-1 ratio in patients with
STEMI than NSTEACS may explain the role of serum MMP-9/TIMP-1 ratio
in differentiating the pathogenesis of STEMI and NSTE-ACS.
(J Kardiol Indones. 2013;34:160-6)
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References
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the management of patients with acute myocardial infarction. A
report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol,
1999;34:890 –911.
Koenig, W., Khuseyinova, N. Biomarkers of Atherosclerotic
Plaque Instability and Rupture. Arterioscler. Thromb. Vasc. Biol.
2007;27:15-26.
Ferroni, P., Basili, S., Martini. F., Cardarello, C. M., Ceci, F.,
Di Franco, M., Bertazzoni, G., Gazzaniga, P. P., Alessandri, C.
Serum metalloproteinase 9 levels in patients with coronary artery
disease: a novel marker of inflammation. J Investig Med., 2003;
51(5):295-300.
Yan, J. C., Wu, Z, G., Kong, X. T., Zong, R. Q., Zhan, L. Z.
Relation between upregulation of CD40 system and compelx
stenosis morphology in patients with acute coronary sysdrome.
Acta Pharmacol Sin. 2004; 25(2):251-256.
Newby, A. Dual Role of Matrix Metalloproteinases (Matrixins)
in Intimal Thickening and Atherosclerotic Plaque Rupture.
Physiol Rev,2005;85:1-31.
Cheng,M., Hashmi, S., Mao, X., Zeng, Q.T. Relationships of
adiponectin and matrix metalloproteinase-9 to tissue inhibitor
of metalloproteinase-1 ratio with coronary plaque morphology
in patients with acute coronary syndrome. Can J Cardiol. 2008;
24(5):385-390
Tan, J., Hua, Q., Gao, J., Fan, Z. X. Clinical Implications
of Elevated Serum Interleukin-6, Soluble CD40 Ligand,
Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinase-
1 in Patients with Acute ST-segment Elevation Myocardial
Infarction. Clin. Cardiol. 2008;31(9):413-418.
Kai, H., Ikeda, H., Yasukawa, H., Kai, M., Seki, Y., Kuwahara,
F., Ueno, T., Sugi, K., Imaizumi, T. Peripheral blood levels of
matrix metalloproteases-2 and -9 are elevated in patients with acute
coronary syndromes. J Am Coll Cardiol, 1998;32(2):368-372.
Manginas, A., Bei, E., Chaidaroglou, A., Degiannis, D.,
Koniaviaton, K., Voudris, V., Pavlides, G., Panagiotakos, D.,
Cokkinos, D.V. Peripheral levels of matrix metalloproteinase-9,
interleukin-6, and C-reactive protein are elevated in patients
with acute coronary syndromes: correlations with serum
troponin I. Clin Cardiol. 2005;28(4):182-186.
Inokubo, Y., Hanada, H., Ishizaka, H., Fukushi, T., Kamada,
T., Okumura, K.Plasma levels of matrix metalloproteinase-9
and tissue inhibitor of metalloproteinase-1 are increased in the
coronary circulation in patients with acute coronary syndrome.
Am Heart J. 2001;141:211-7.
Thompson, M.M., Squire, I.B. Matrix metalloproteinase-9
expression after myocardial infarction: physiological or pathological?. Cardiovascular Research. 2002;54:495-498
Romanic, A.M., Harrison, S.M., Bao, W., Burns-Kurtis, C.L.,
Pickering, S., Gu, Garu, E., Mao, J., Sathe, G.M., Ohlstein,
E.H., Yue, T.L. Myocardial protection from ischemia/ reperfusion
injury by targeted deletion of matrix metalloproteinase-9.
Cardivascular Research. 2002;54:549-558
Holven, K.B., Aukrust, P., Pedersen, T.M., Ose, L., Nenseter ,
M.S. Enhanced Platelet Activation In Hyperhomocysteinemic
Individuals, Journal of Thrombosis and Haemostasis. 2006.
Volume 5, Issue 1, pages 193–195
Libby, P.The Vascular Biology of Atherosclerosis. In Zipes, D.P.,
Libby, P., Bonow, R.O., Braunwald, E (ed.), Braunwald’s Heart
Disease: A Textbook os Cardiovascular Medicine. 2006.Elseviern
Saunders, Vol. 2: pp. 921-958.
Published
2014-03-25
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How to Cite
Rahmat, B., Dinarti, L., I, I., & Setianto, B. (2014). Differences of Serum Ratio MMP-9/TIMP-1 in ST-Elevation Myocardial Infarction (STEMI) and Non ST-Elevation Acute Coronary Syndrome (NSTEACS). Indonesian Journal of Cardiology, 34(3), 160-6. https://doi.org/10.30701/ijc.v34i3.337
Section
Clinical Research
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