Objective
The aim of this study was to evaluate the levels of matrix metalloproteinase-12 (MMP-12)
and tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2, TIMP-3, and TIMP-4 in
patients with symptomatic and asymptomatic critical carotid artery stenosis (CAS).
Methods
We enrolled 10 patients affected by symptomatic CAS within 12 hours from onset of
stroke (S group) and 30 patients with asymptomatic CAS (CAS group); 31 patients matched
for age, sex, and traditional cardiovascular risk factors were used as controls (RF
group). Serum levels of MMP-12, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 were assessed by
Luminex.
Results
MMP-12 levels were significantly higher both in the S and CAS groups than in the RF
group (P < .001). We found a significant decrease of all TIMPs in the CAS group compared with
the RF group, whereas a significant increase was observed in the S group compared
with the CAS group. A significant increase of TIMP-3 and TIMP-4 levels was observed
in the S group compared with all other groups.
Conclusion
MMP-12 is related to critical CAS both symptomatic and asymptomatic, being mainly
released in the late stage of plaque development. Moreover, we suggest that a specific
pattern of matrix degrading enzyme inhibitors arises during the early phases of stroke.
Key Words
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References
- The role of monocytes in ischemic stroke pathobiology: new avenues to explore.Front Aging Neurosci. 2016; 8 (eCollection 2016. Review): 29https://doi.org/10.3389/fnagi.2016.00029
- Inflammation, atherosclerosis and coronary artery disease.N Engl J Med. 2005; 352: 1685-1695
- The many role of chemokines and chemokine receptors in inflammation.N Engl J Med. 2006; 354: 610-621
- Executive summary: heart disease and stroke statistics—2016 update a report from the American Heart Association.Circulation. 2016; 133: 447-454
- Matrix metalloproteinases and atherosclerotic plaque instability.Br J Surg. 2002; 89: 680-694
- Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo.Blood. 2002; 100: 1160-1167
- Stanford-A acute aortic dissection, inflammation, and metalloproteinases: a review.Ann Med. 2015; 47: 441-446
- Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease.EXS. 2012; 103: 209-279
- Matrix metalloproteinases as therapeutic targets for stroke.Brain Res. 2015; 1623: 30-38
- Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability.Nucl Med Biol. 2014; 41: 562-569
- Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics.Stroke. 2004; 35: 1310-1315
- Low elastin content of carotid plaque is associated with increased risk of ipsilateral stroke.PLoS ONE. 2015; 10 (eCollection 2015): e0121086https://doi.org/10.1371/journal.pone.0121086
- Correlation between MMP-9 and extracellular cytokine HMGB1 in prediction of human ischemic stroke outcome.Biochim Biophys Acta. 2014; 1842: 1379-1384
- Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke.Neurology. 2006; 66: 1550-1555
- Polymorphism in matrix metalloproteinase-1,-3,-9, and -12 genes in relation to subarachnoid hemorrhage.Stroke. 2001; 32: 2198-2202
- Metalloproteinases promote plaque rupture and myocardial infarction: a persuasive concept waiting for clinical translation.Matrix Biol. 2015; 44-46: 157-166
- MMP-12 as a new marker of Stanford-A acute aortic dissection.Ann Med. 2014; 46: 44-48
- Management strategies for asymptomatic carotid stenosis: a systematic review and meta-analysis.Ann Intern Med. 2013; 158: 676-685
- MMP-12 has a role in abdominal aortic aneurysms in mice.Surgery. 2005; 137: 457-462
- Carotid atherosclerotic plaque matrix metalloproteinase-12-positive macrophage subpopulation predicts adverse outcome after endarterectomy.J Am Heart Assoc. 2012; 1: e001040https://doi.org/10.1161/JAHA.112.001040
- A novel MMP-12 locus is associated with large artery atherosclerotic stroke using a genome- wide age-at onset informed approach.PLoS Genet. 2014; 10: e1004469
- Matrix metalloproteinase 12 accelerates the initiation of atherosclerosis and stimulates the progression of fatty streaks to fibrous plaque in transgenic rabbits.Am J Pathol. 2008; 172: 1419-1429
- Pathology of the vulnerable plaque.J Am Coll Cardiol. 2006; 47: C13-C18
- Matrix metalloproteinase-12 induces blood brain barrier damage after focal cerebral ischemia.Stroke. 2015; 46: 3523-3531
- Post transcriptional inactivation of matrix metalloproteinase 12 after focal cerebral ischemia attenuates brain damage.Sci Rep. 2015; 5: 9504
- The multitasking role of macrophages in Stanford type A acute aortic dissection.Cardiology. 2014; 127: 123-129
- Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice.Arterioscler Thromb Vasc Biol. 2003; 23: 1621-1626
- MMP-12 deficiency attenuates angiotensin II-induced vascular injury, M2 macrophage accumulation, and skin and heart fibrosis.PLoS ONE. 2014; 9 (e109763)
- Loss of TIMP-3 exacerbates atherosclerosis in apoE null mice.Atherosclerosis. 2014; 235: 438-443
- Tissue inhibitor of metalloproteinases-4 suppresses vascular smooth muscle cell migration and induces cell apoptosis.Life Sci. 2004; 75: 2483-2489
Article info
Publication history
Published online: October 13, 2016
Accepted:
September 15,
2016
Received:
June 21,
2016
Footnotes
Grant support: This study was funded by the Università di Roma “La Sapienza”, Progetto di Ricerca di Università n° C26A147BZP.
Conflict of interest: The authors have no actual or potential conflict of interest to declare, including any financial, personal, or other relationships with other people or organizations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.09.025
Copyright
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
