Sirolimus-Eluting Stents Associated With Paradoxic Coronary Vasoconstriction

Togni, Mario; Windecker, Stephan; Cocchia, Rosangela; Wenaweser, Peter; Cook, Stéphane; Billinger, Michael; Meier, Bernhard; Hess, Otto M.

doi:10.1016/j.jacc.2005.01.062

Cited by 345 publications

(220 citation statements)

References 31 publications

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“…19 Consistent with this observations, inhibition of mTOR delays EC senescence in vivo 21 and in vitro, 22 improves vascular outcomes of stroke, 23,24 and has been shown to have EC-dependent vasodilatory effects. 25,26 Although distal EC dysfunction has been observed with rapamycin-eluting stents implanted in coronary heart disease patients, 27,28 recent studies have shown that this effect may be due to delayed or absent re-endothelization of the stent, 29 or to effects of the stent itself. 30 We and others have shown that, consistent with its lifespan-extending effects, reduction of mTOR activity by chronic rapamycin treatment halts the progression of AD-like memory deficits and reduces Ab accumulation in mouse models of the disease 31,32 when administered before the onset of robust cognitive deficits.…”

Section: Introductionmentioning

confidence: 99%

Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease

Lin¹,

Zheng

Halloran

et al. 2013

J Cereb Blood Flow Metab

176

201

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Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.

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Section: Introductionmentioning

confidence: 99%

Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease

Lin¹,

Zheng

Halloran

et al. 2013

J Cereb Blood Flow Metab

176

201

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“…Moreover, early generation DES have been associated with endothelial dysfunction (8) and an increased risk of neoatherosclerosis (9) compared with bare metal stents. Delayed vascular healing after implantation of early generation DES may not only be the underlying mechanism of very late stent thrombosis, but also explain the catch-up phenomenon of delayed late loss observed during long-term angiographic follow after DES implantation (10).…”

Section: Introductionmentioning

confidence: 99%

Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial

Pilgrim¹,

Roffi

Tüller

et al. 2014

American Heart Journal

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Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial, American Heart Journal (2014), doi: 10.1016/j.ahj.2014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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“…21 Togni and colleagues evaluated coronary vasomotion with biplane quantitative coronary angiography at rest and during supine bicycle exercise in patients with coronary artery disease who were treated with PES, SES and BMS. 22,23 Both DES were associated with paradoxic exercise-induced vasoconstriction of the adjacent vessel segments. Shin and colleagues also showed that SES and PES implantation were associated with endothelial dysfunction at six to nine months, predominantly in the distal segment of the treated vessel.…”

Section: Des-induced Endothelial Dysfunctionmentioning

confidence: 99%

Late stent thrombosis, endothelialisation and drug-eluting stents

Ertaş

Beusekom²,

Giessen³

2009

NHJL

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Drug-eluting stents (DES) significantly reduce the risk of restenosis after percutaneous coronary revascularisation, but an increased risk of late stent thrombosis (LST) has been put forward as a major safety concern. Meta-analysis of clinical trials, however, does not support this caveat. Even so, many interventional cardiologists think that LST is associated with DES and related to delayed endothelialisation. This hypothesis is based on autopsy studies and clinical intracoronary angioscopy. In autopsy studies, differences between endothelialisation of DES and baremetal stents (BMS) have been reported. Most preclinical studies, however, have failed to show any significant differences in endothelialisation between DES and BMS. Our own studies, using the porcine coronary artery model, also suggest that DES show no differences in re-endothelialisation. However, DES do delay vascular healing and induce endothelial dysfunction. This paper will review clinical and animal studies which consider re-endothelialisation and LST. (Neth Heart J 2009;17:177-81.)Keywords: drug-eluting stents, stent thrombosis, endothelium, endothelial function P olymer-based sirolimus (SES) and paclitaxel (PES) eluting coronary stents have reduced rates of restenosis and late lumen loss compared with bare-metal stents (BMS), resulting in a significant reduction in the need for target vessel revascularisation. 1,2 Delayed healing and more specifically delayed re-endothelialisation after drug-eluting stent (DES) implantation have been suggested as the cause of late stent thrombosis (LST, defined as thrombosis ≥30 days after stent deployment). 3 This concept is based on clinical autopsy studies and clinical intracoronary angioscopy studies. 4,5 However we feel this concept is still open to debate. Our hypothesis is that delayed re-endothelialisation alone is not adequate to explain LST. The pathogenesis of LST is still not completely understood, and may be affected by a combination of factors. The present review discusses possible pathophysiological mechanisms of stent thrombosis in DES. DES induced late stent thrombosis, clinical studiesRecent reports from randomised trials suggest that some DES may be associated with increased rates of LST as compared with BMS. Stone et al. reported that both SES and PES were associated with a significant increase in the incidence of LST between one and four years after implantation (0.6 and 0.7%), as compared with BMS (0.2%). 6 Stettler and colleagues suggested that there is no evidence of an overall increase in definite stent thrombosis associated with SES between one and four years (0.3 vs. 0.2% in BMS). 7 However, the risk of LST seemed to be increased with PES (0.6%) with a significantly increased hazard ratio (2.1, p=0.017 vs. BMS between day 0 and 4 years). Garg and colleagues reported a small increase in DES thrombosis compared with BMS after one year (>0.14%/year). 8 This rate is, however, considerably lower than that reported by Daemen and Wenaweser and colleagues, who found that LST occurs in both D...

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Sirolimus-Eluting Stents Associated With Paradoxic Coronary Vasoconstriction

Cited by 345 publications

References 31 publications

Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease

Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease

Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial

Late stent thrombosis, endothelialisation and drug-eluting stents

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