Drug-eluting stents: new era and new concerns

Bhatia, Vineet; Bhatia, Ravi; Dhindsa, Mandeep

doi:10.1136/pmj.2003.009431

Cited by 44 publications

(19 citation statements)

References 47 publications

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“…Although the introduction of drugeluting stents has im proved the prevention and treatment of restenosis (Iakovou et al, 2005), an 8-17% neointimal obstruction persists in most cases (Waseda et al, 2009). Moreover, the entrapped immuno suppressive and cytostatic agents are relatively nonspecific (Marx and Marks, 2001;Bhatia et al, 2004) and are associated with latestent thrombosis (Iakovou et al, 2005). Regarding human AAA, surgical repair is considered appropriate for large aneurysms, but the overall 30d mortality is 5% (Sakalihasan et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

Esteban¹,

Jiménez-Borreguero²,

Roqué³

et al. 2011

J Cell Biol

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Section: Discussionmentioning

confidence: 99%

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

Esteban¹,

Jiménez-Borreguero²,

Roqué³

et al. 2011

J Cell Biol

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“…1,2 The introduction of drugeluting stents has been a true breakthrough in the prevention and treatment of restenosis, but the entrapped immunosuppressive and cytotoxic agents are relatively unspecific and can lead to adverse effects in flanking regions and to impaired vessel functionality. 3,4 Given the inflammatory nature of restenosis, it is conceivable that more specific anti-inflammatory compounds may display a more favorable activity profile.…”

mentioning

confidence: 99%

Therapeutic Potential of a Synthetic Peptide Inhibitor of Nuclear Factor of Activated T Cells as Antirestenotic Agent

Sliedregt-Bol

Overkleeft

et al. 2006

ATVB

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Objective-The calcineurin/nuclear factor of activated T cells (NFAT) axis plays a pivotal role in the regulation of critical genes in vascular smooth muscle cell (vSMC) proliferation and inflammation, which makes NFAT inhibition an attractive modality in the prevention of restenosis. Methods and Results-Synthetic peptide VIVIT potently inhibited NFAT activation in RAW 264.7 macrophages, Ea.Hy.926 endothelial cells and vSMCs, and blocked ionomycin-elicited nuclear import of NFAT. VIVIT, as well as cyclosporine A (CsA) or FK506, completely blunted platelet-derived growth factor-BB (PDGF-BB) and thrombininduced vSMC proliferation. Moreover, it significantly inhibited PDGF-BB and thrombin-induced interleukin-6, interleukin-8, transforming growth factor-␤1, stromal cell-derived factor-1␣, and monocyte chemotactic protein-1 expression in vSMCs. Unlike FK506 or CsA, VIVIT did not affect nuclear factor B reporter gene activation and did only marginally affect endothelial wound healing in vitro. VIVIT did not intervene in phorbol 12-myristate 13-acetate-stimulated extracellular signal-regulated kinase activation, confirming its specificity for NFAT. Furthermore, our data establish that NFAT is a regulator of PDGF-BB induced vSMC proliferation. Conclusions-VIVIT appears to be a specific and potent inhibitor of NFAT activation and thus of NFAT-mediated proliferation and inflammation. Unlike FK506 or CsA, synthetic VIVIT therapy will not be accompanied by non-NFAT-mediated side effects on calcineurin signaling and constitutes a promising lead in antirestenotic therapy.

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“…Although it has not been shown conclusively that the excellent initial and midterm results of DES will persist in the long term, 32,33 as opposed to delaying the onset of ISR, current evidence supports their efficacy. 34 DES reduce both angiographically determined ISR rates from one third in patients with bare metals stents to Ͻ10% 32 and the rate of major adverse cardiac events.…”

Section: Discussionmentioning

confidence: 90%

Elevated Plasma Active Matrix Metalloproteinase-9 Level Is Associated With Coronary Artery In-Stent Restenosis

Jones

Kay

Chu

et al. 2006

ATVB

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Objective-This study aimed to determine whether the plasma levels of matrix metalloproteinase-9 (MMP-9) or tissue inhibitor of metalloproteinases-1 (TIMP-1) were altered in patients with a history of symptomatic in-stent restenosis (ISR). Methods and Results-A group of 158 patients with a history of ISR were compared with 128 symptom-free patients.Plasma samples and a detailed risk factor history were collected. Plasma samples were analyzed for pro-MMP-9 and latent MMP-9 and active MMP-9, latent MMP-3, and TIMP-1. Several variables were associated with ISR, including index coronary disease extent and severity (number of diseased vessels and American College of Cardiology/American Heart Association lesion classification), number, diameter, and total length of stent(s) inserted, and plasma high-density lipoprotein cholesterol. Plasma active MMP-9 (odds ratio, 1.96; 95% CI, 1.43 to 2.69) showed independent risk association with ISR. Patients with multiple sites of ISR had significantly higher levels of active MMP-9 compared with patients with only a single ISR lesion or no ISR. Conclusion-Plasma active MMP-9 levels may be a useful independent predictor of bare metal stent ISR. Key Words: plasma Ⅲ MMP-9 Ⅲ TIMP-1 Ⅲ restenosis V ascular connective tissue remodeling is a wellrecognized ubiquitous process that occurs after percutaneous coronary interventions including intracoronary stent placement. 1 Mechanical injury has been shown to induce collagenase and stromelysin gene expression in cultured smooth muscle 2 and an increase in gelatinase activity after balloon catheter injury to the rat carotid. 3,4 Overexpression of the gelatinase matrix metalloproteinase-9 (MMP-9) has been shown to enhance smooth muscle cell (SMC) migration within in vitro assays. Moreover, the levels of various MMPs appear to be associated with postinterventional vascular remodeling in human blood vessels. 5-10 Such in vitro and in vivo findings suggest that increased levels of MMPs in coronary arteries undergoing percutaneous intervention may be associated with vascular remodeling and restenosis by promoting migration of vascular SMCs.In this study, the circulating plasma levels of pro-MMP-9, latent MMP-9 and active MMP-9, latent MMP-3, and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated in patients who had previously undergone bare metal coronary stent placement. Patients were subdivided into those who developed symptomatic, angiographically proven, instent restenosis (ISR) and those who were (angina) symptomfree for Ͼ1 year after their stent placement. Materials and Methods SubjectsPatients with coronary bare-metal stent placements were recruited retrospectively from the Dunedin Hospital Cardiology Clinical database. A group of 158 consecutive patients with a history of symptomatic, angiographically proven, ISR (coronary artery disease [CAD] with ISR) were compared with a consecutive series of 128 patients who were angina-free for Ͼ1 year after their stent placement (CAD with stent). The CAD with ISR group included patien...

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Drug-eluting stents: new era and new concerns

Cited by 44 publications

References 47 publications

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

Therapeutic Potential of a Synthetic Peptide Inhibitor of Nuclear Factor of Activated T Cells as Antirestenotic Agent

Elevated Plasma Active Matrix Metalloproteinase-9 Level Is Associated With Coronary Artery In-Stent Restenosis

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