Association study of matrix metalloproteinase 3 5A/6A polymorphism
with in-stent restenosis after percutaneous coronary interventions in a Han
Chinese population

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Abstract

Objective

We aimed to investigate the association between the 5A/6A promoter polymorphism in the matrix metalloproteinase 3 ( MMP3) gene and in-stent restenosis (ISR) in a regional Chinese population.

Methods

A total of 818 patients who underwent primary implantation of drug-eluting stents were enrolled and received a 6-month follow-up angiography and DNA genotyping of the 5A/6A polymorphism.

Results

ISR was found in 36.9% of all patients (302 ISR vs. 516 no ISR). The genotype proportion of 6A6A was significantly increased in ISRs (74.2% ISR vs. 66.8% no ISR), whereas the allele frequency of 5A was significantly decreased in ISR patients (25.8%) compared with controls who did not undergo ISR (33.1%).

Conclusions

Our data indicate that the MMP3 6A6A genotype is a genetic susceptibility factor for ISR after coronary stent placement, but the 5A allele can lower the risk for patients within 6 months after stenting. Therefore, genotyping 5A/6A in the MMP3 promoter is suggested for patients who undergo coronary stent implantation.

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Most cited references 36

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Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.

Z. Galis, G Sukhova, M Lark … (1994)

Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention.

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A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group.

Patrick W. Serruys, Peter P.T.h. de Jaegere, Ferdinand Kiemeneij … (1994)

Balloon-expandable coronary-artery stents were developed to prevent coronary restenosis after coronary angioplasty. These devices hold coronary vessels open at sites that have been dilated. However, it is unknown whether stenting improves long-term angiographic and clinical outcomes as compared with standard balloon angioplasty. A total of 520 patients with stable angina and a single coronary-artery lesion were randomly assigned to either stent implantation (262 patients) or standard balloon angioplasty (258 patients). The primary clinical end points were death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for coronary-artery bypass surgery, or a second percutaneous intervention involving the previously treated lesion, either at the time of the initial procedure or during the subsequent seven months. The primary angiographic end point was the minimal luminal diameter at follow-up, as determined by quantitative coronary angiography. After exclusions, 52 patients in the stent group (20 percent) and 76 patients in the angioplasty group (30 percent) reached a primary clinical end point (relative risk, 0.68; 95 percent confidence interval, 0.50 to 0.92; P = 0.02). The difference in clinical-event rates was explained mainly by a reduced need for a second coronary angioplasty in the stent group (relative risk, 0.58; 95 percent confidence interval, 0.40 to 0.85; P = 0.005). The mean (+/- SD) minimal luminal diameters immediately after the procedure were 2.48 +/- 0.39 mm in the stent group and 2.05 +/- 0.33 mm in the angioplasty group; at follow-up, the diameters were 1.82 +/- 0.64 mm in the stent group and 1.73 +/- 0.55 mm in the angioplasty group (P = 0.09), which correspond to rates of restenosis (diameter of stenosis, > or = 50 percent) of 22 and 32 percent, respectively (P = 0.02). Peripheral vascular complications necessitating surgery, blood transfusion, or both were more frequent after stenting than after balloon angioplasty (13.5 vs. 3.1 percent, P < 0.001). The mean hospital stay was significantly longer in the stent group than in the angioplasty group (8.5 vs. 3.1 days, P < 0.001). Over seven months of follow-up, the clinical and angiographic outcomes were better in patients who received a stent than in those who received standard coronary angioplasty. However, this benefit was achieved at the cost of a significantly higher risk of vascular complications at the access site and a longer hospital stay.

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A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators.

David L Fischman, Martin Leon, Donald S Baim … (1994)

Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes. We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later. The patients who underwent stenting had a higher rate of procedural success than those who underwent standard balloon angioplasty (96.1 percent vs. 89.6 percent, P = 0.011), a larger immediate increase in the diameter of the lumen (1.72 +/- 0.46 vs. 1.23 +/- 0.48 mm, P < 0.001), and a larger luminal diameter immediately after the procedure (2.49 +/- 0.43 vs. 1.99 +/- 0.47 mm, P < 0.001). At six months, the patients with stented lesions continued to have a larger luminal diameter (1.74 +/- 0.60 vs. 1.56 +/- 0.65 mm, P = 0.007) and a lower rate of restenosis (31.6 percent vs. 42.1 percent, P = 0.046) than those treated with balloon angioplasty. There were no coronary events (death; myocardial infarction; coronary-artery bypass surgery; vessel closure, including stent thrombosis; or repeated angioplasty) in 80.5 percent of the patients in the stent group and 76.2 percent of those in the angioplasty group (P = 0.16). Revascularization of the original target lesion because of recurrent myocardial ischemia was performed less frequently in the stent group than in the angioplasty group (10.2 percent vs. 15.4 percent, P = 0.06). In selected patients, placement of an intracoronary stent, as compared with balloon angioplasty, results in an improved rate of procedural success, a lower rate of angiographically detected restenosis, a similar rate of clinical events after six months, and a less frequent need for revascularization of the original coronary lesion.

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Author and article information

Journal

Journal ID (nlm-ta): J Int Med Res

Journal ID (iso-abbrev): J. Int. Med. Res

Journal ID (publisher-id): IMR

Journal ID (hwp): spimr

Title: The Journal of International Medical Research

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 0300-0605

ISSN (Electronic): 1473-2300

Publication date (Electronic): 8 February 2019

Publication date Collection: January 2020

Volume: 48

Issue: 1

Electronic Location Identifier: 0300060519827145

Affiliations

[1 ]Department of Cardiovascular Medicine, Tianjin Cardiovascular Disease Institute, Tianjin Chest Hospital, Tianjin, People’s Republic of China

[2 ]Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, People’s Republic of China

[3 ]Department of Gynecology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin Medical University, Tianjin, People’s Republic of China

[4 ]Department of Pathology, Xingtai Medical College, Xingtai, Hebei, People’s Republic of China

Author notes

[*]Yi-Liang Wei, Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Qixiangtai Road 22, Heping District, Tianjin, 300070, People’s Republic of China. Email: yiliangwei@ 123456yahoo.com

Author information

Yi-Liang Wei https://orcid.org/0000-0001-5751-9637

Article

Publisher ID: 10.1177_0300060519827145

DOI: 10.1177/0300060519827145

PMC ID: 7140217

PubMed ID: 30732526

SO-VID: f17f6433-4f71-4bf9-9b26-379311b034fa

License:

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 28 August 2018

Date accepted : 7 January 2019

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Keywords: percutaneous coronary intervention,in-stent restenosis,extracellular matrix,matrix metalloproteinase-3,5a/6a promoter polymorphism,han chinese population,drug-eluting stent

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Keywords: percutaneous coronary intervention, in-stent restenosis, extracellular matrix, matrix metalloproteinase-3, 5a/6a promoter polymorphism, han chinese population, drug-eluting stent

Association study of matrix metalloproteinase 3 5A/6A polymorphism with in-stent restenosis after percutaneous coronary interventions in a Han Chinese population

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Abstract

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Conclusions

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International Journal of Medicine and Medical Research

Most cited references 36

Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.

A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group.

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators.

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