Increased Restenosis Rate After Implantation of Drug-Eluting Stents in Patients With Elevated Serum Activity of Matrix Metalloproteinase-2 and -9

Katsaros, Katharina M.; Kastl, Stefan P.; Zorn, Gerlinde; Maurer, Gerald; Wojta, Johann; Huber, Kurt; Christ, Günter; Speidl, Walter S.

doi:10.1016/j.jcin.2009.10.023

Cited by 40 publications

(36 citation statements)

References 25 publications

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“…18 MMP-2 and MMP-9 are well known to play fundamental roles in the migration of vascular SMCs and matrix remodeling during wound healing and are produced by vascular SMCs, endothelial cells, macrophages, lymphocytes, and mast cells in response to mechanical injury. Significant elevations in MMP-9 levels at baseline and MMP-2 and MMP-9 levels 24 hours post-percutaneous coronary intervention have proven to be strongly associated with the development of ISR following DES implantation.…”

Section: Serum Matrix Metalloproteinase (Mmp) Activity and Geneticsmentioning

confidence: 99%

“…Conversely low and nearnormal MMP-2 and MMP-9 levels were associated with a lack of a significant restenotic response. 18 Gene polymorphisms linked with the inflammatory response have been found to be associated with ISR. 19 As examples, homozygosity of the 16/glycine variant in the ␤ 2 -adrenergic receptor (a mediator of nitrous oxide synthetase) has been associated with ␤ 2 -adrenergic receptor downregulation and an increased risk of restenosis 19 ; Vogiatizi et al 20 described a 15-fold increase in the risk of restenosis associated with 2 functional polymorphisms of interleukin-8 (a strong mediator of inflammation).…”

Section: Serum Matrix Metalloproteinase (Mmp) Activity and Geneticsmentioning

confidence: 99%

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Restenosis

Farooq

Gogas

Serruys

2011

Circ: Cardiovascular Interventions

167

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In the past decade, tremendous progress has been made in reducing the incidence of restenosis with the advent of the drug-eluting stent (DES). With "plain old balloon angioplasty," rates of acute and chronic vessel occlusion were unacceptably high at Ϸ30% to 60%, secondary to acute and chronic recoil and constrictive remodeling. The advent of bare-metal stents (BMS) appeared to eliminate the issue of acute and chronic recoil but introduced a new entity, neointimal hyperplasia (NIH), with classical papers unequivocally demonstrating a strong and linear relationship between NIH formation and late lumen loss (LLL). The restenosis rates with BMS were reported to be between 16% and 44%, with higher rates of stenosis attributable to several risk factors, in particular, long lesion length and small vessel caliber. 1 DES were thus conceived as the next step in tackling this iatrogenic entity of NIH, with large-scale reductions in restenosis rates reported at 0% in highly selective lesions and up to 16% in a broader range of patients and lesions with first-generation DES. 1 In contrast to plain old balloon angioplasty and BMS, in which an almost classical gaussian distribution of LLL is seen postprocedurally, the LLL after DES implantation appears to follow a bimodal pattern of distribution ( Figure 1). 2 Despite the significant advances in the technology to reduce DES restenosis, conservative estimates still suggest that the incidence of in-stent restenosis (ISR) requiring target vessel revascularization (TVR), so-called DES failure, to be Ϸ5% to 10%, with one estimate suggesting Ϸ200 000 repeat revascularizations in the United States alone. 3 Whereas the pattern of restenosis in BMS has been shown to be primarily diffuse, with DES it has been demonstrated to be usually focal ( Figure 2) and most commonly located at the proximal DES edge, as demonstrated in Ͼ60% of ISR with either paclitaxel-eluting stent (PES) or sirolimus-eluting stent (SES) implantation. However, over one-fifth of ISR cases remain diffuse, and 10% to 20% are even occlusive. 4 In 2004, the first report of risk factors associated with DES restenosis in patients with the unrestricted use of SES since approval of its CE mark was made by our group. Despite the apparent differences in the distribution of LLL between BMS and DES as previously described, the main message of these and subsequent findings was that the usual patient characteristics, lesion types, and procedural factors incriminated with restenosis in BMS were equally responsible with DES, with diabetes mellitus implicated as one of the strongest risk factors. It should however be emphasized that the "slope" of the distribution of restenosis with DES appears to be much flatter compared with BMS, especially in long lesions and small vessels, highlighting the importance of drug elution in potentially attenuating the NIH response. 3 Histopathologic analyses of in-stent neointima taken by directional atherectomy at the time of reintervention also have been shown to be remarkably similar between BMS ...

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Section: Serum Matrix Metalloproteinase (Mmp) Activity and Geneticsmentioning

confidence: 99%

Section: Serum Matrix Metalloproteinase (Mmp) Activity and Geneticsmentioning

confidence: 99%

Restenosis

Farooq

Gogas

Serruys

2011

Circ: Cardiovascular Interventions

167

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“…A mechanical injury induces expression of matrix metalloproteinases (MMP), and there is some evidence that they may play a role in the pathogenesis of ISR (ref. [9][10][11][12] ). We found that increased levels of MMP-3 and 9 were associated with a significant increase in ISR risk.…”

Section: Matrix Metalloproteinases (Mmps) Comprise a Family Of Zinc-dmentioning

confidence: 99%

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency

Pleva¹,

Kušnierová²,

Plevová³

et al. 2015

BIOMED PAP

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Aims. We sought to identify biochemical predictors that indicate susceptibility to in-stent restenosis (ISR) after coronary artery bare-metal stenting. Methods. A total of 111 consecutive patients with post-percutaneous coronary intervention (PCI) in-stent restenosis of a target lesion within 12 months were matched for age, sex, vessel diameter, and diabetes with 111 controls without post-PCI ISR. Plasma or serum levels of biochemical markers were measured: matrix metalloproteinases (MMP) 2, 3, 9; myeloperoxidase (MPO); asymmetric dimethylarginine (ADMA); lipoprotein (a) (Lp[a]); apolipoproteins E and D (ApoE and D); and lecitin-cholesterol acyltransferase (LCAT). Multivariable logistic regression association tests were performed. Results. Increased plasma MMP-3 (OR: 1.013; 95% CI: 1.004-1.023; P = 0.005), MMP-9 (OR: 1.014; 95% CI: 1.008-1.020; P < 0.0001) or MPO (OR: 1,003; 95% CI: 1.001-1.005; P = 0.002) was significantly associated with increased risk of ISR. Increased levels of ADMA (OR: 0.212; 95% CI: 0.054-0.827; P = 0.026), ApoE (OR: 0.924; 95% CI: 0.899-0.951; P < 0.0001), ApoD (OR: 0.919; 95% CI: 0.880-0.959; P = 0.0001), or LCAT (OR: 0.927; 95% CI: 0.902-0.952; P < 0.0001) was associated with risk reduction. No correlation was found between plasma MMP-2 or Lp (a) and ISR risk. Conclusions. Increased levels of MMP-3, MMP-9, and MPO represent predictors of ISR after bare-metal stent implantation. In contrast, increased ADMA, LCAT, and Apo E and D indicate a decreased in-stent restenosis occurrence.

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“…A mechanical damage causes expression of matrix metalloproteinases (MMP), and it is proved that they may take part in the pathogenesis of in-stent restenosis (ISR), when undergoing coronary stent implantation by percutaneous coronary intervention [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases MMP-3 and MMP-9 as Predictors of In-Stent Restenosis

Kušnierová¹,

Pleva²

2017

The Role of Matrix Metalloproteinase in Human Body Pathologies

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The present study aimed to demonstrate the use of matrix metalloproteinases (MMP-2, MMP-3 and MMP-9) as possible additional biochemical predictors of in-stent restenosis (ISR) and determined their reference intervals in adults with respect to gender and age. We included 111 consecutive patients treated at the cathlab of the University Hospital Ostrava, Czech Republic, with ISR within 12 months after implantation of a bare-metal stent. The control group consisted of 111 matched patients with identical main demographic and clinical risk factors. To set the reference intervals for MMPs, we measured the blood concentrations of these analytes in a group of healthy volunteers (N = 180) with an average age of 40-50 years. The enzyme concentrations were measured by immunosorbent assay. Statistical analysis was performed using IBM SPSS Statistics version 22 and MedCalc Version 14.12. We found that increased levels of MMP-3 and 9 were associated with a signiicant increase in ISR risk. The MMP-9 cut-of value for ISR risk prediction was determined to be ≥64.8 ng/mL. We suppose that screening of these biochemical parameters might be helpful to a more detailed risk stratiication of patients after percutaneous coronary interventions, who would be able to beneit from implantation of drug-eluting stents.

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Increased Restenosis Rate After Implantation of Drug-Eluting Stents in Patients With Elevated Serum Activity of Matrix Metalloproteinase-2 and -9

Abstract: Elevated serum activities of MMP-2 and -9 are associated with dramatically increased restenosis rates after PCI with implantation of DES. Determination of MMP levels might be useful for identification of patients who are at high risk for ISR despite implantation of DES.

Cited by 40 publications

References 25 publications

Restenosis

Restenosis

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency

Matrix Metalloproteinases MMP-3 and MMP-9 as Predictors of In-Stent Restenosis

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