The Effects of Paclitaxel on the Three Phases of Restenosis

Wiskirchen, Jakub; Schöber, Wolfgang; Schart, Nadine; Kehlbach, Rainer; Wersebe, Annika; Tepe, Gunnar; Claussen, Claus D.; Duda, Stephan H.

doi:10.1097/01.rli.0000133815.22434.55

Cited by 57 publications

(18 citation statements)

References 41 publications

(28 reference statements)

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“…While sirolimus and paclitaxel reduce neointimal formation by decreasing smooth muscle cell proliferation and migration, these drugs also impair the normal healing process of the injured arterial wall [13–15]. Underlying plaque morphology also affects the rate of healing when stent struts penetrate deeply into a necrotic core [16].…”

Section: Endothelial Coverage: the Most Important Morphometric Prementioning

confidence: 99%

Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement

et al. 2012

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Several randomized and observational studies have reported steady increase in cumulative incidence of late and very late ST (LST/VLST) following first-generation drug-eluting stents (DES: sirolimus-(SES) and paclitaxel-(PES)) up to 5 years. Pathologic studies have identified uncovered struts as the primary substrate responsible for LST/VLST following DES, where delayed arterial healing is associated with stent struts penetrating into the necrotic core, long/overlapping stents, and bifurcation stenting especially in flow divider region. Grade V stent fracture also induces LST/VLST and restenosis. Hypersensitivity reaction is exclusive to SES as an etiology of LST/VLST, whereas malapposition secondary to excessive fibrin deposition is associated with PES. Uncovered struts can be identified in SES and PES with duration of implant beyond 12 months, particularly in stents placed for “off-label” indications. Neoatherosclerosis is another important contributing factor for VLST in DES and bare metal stents (BMS); however, DES shows rapid and more frequent development of neoatherosclerosis than BMS. Future pathologic studies should address the long-term safety of newer generation DES including zotarolimus- and everolimus-eluting stents in terms of the improvement in reendothelialization, decreased inflammation and fibrin deposition as well as a lower incidence of stent fracture-related adverse events, and reduced neoatherosclerosis, which likely contribute to the decreased risk of LST/VLST and better patient outcomes.

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Section: Endothelial Coverage: the Most Important Morphometric Prementioning

confidence: 99%

Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement

et al. 2012

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“…Paclitaxel, a potent anti-microtubule agent, induces tubulin polymerization and the formation of abnormally stable and nonfunctional microtubles [41], which disrupts the normal cell cycle progression in VSMCs [42, 43] and other cell types [44]. At very low concentrations (10 nM), paclitaxel arrests the cell cycle at the G2/M phase [43, 44], unlike the G1-phase arrest by sirolimus [39]. The paclitaxel-induced cell cycle arrest is often accompanied by apoptosis [45].…”

Section: Discussionmentioning

confidence: 99%

Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration

Pinkaew

Cho

Hui

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background In-stent restenosis, or renarrowing within a coronary stent, is the most ominous complication of percutaneous coronary intervention, caused by vascular smooth muscle cell (VSMC) migration into and proliferation in the intima. Although drug-eluting stents reduce restenosis, they delay the tissue healing of the injured arteries. No promising alternative anti-restenosis treatments are currently on the horizon. Methods & Results In endothelium-denudated mouse carotid arteries, oral morelloflavone—an active ingredient of the Thai medicinal plant Garcinia dulcis—significantly decreased the degree of neointimal hyperplasia, without affecting neointimal cell cycle progression or apoptosis as evaluated by Ki-67 and TUNEL staining, respectively. At the cellular level, morelloflavone robustly inhibited VSMC migration as shown by both scratch wound and invasion assays. In addition, morelloflavone prevented VSMCs from forming lamellipodia, a VSMC migration apparatus. Mechanistically, the inhibition by morelloflavone of VSMC migration was through its negative regulatory effects on several migration-related kinases, including FAK, Src, ERK, and RhoA. Consistently with the animal data, morelloflavone did not affect VSMC cell cycle progression or induce apoptosis. Conclusion These data suggest that morelloflavone blocks injury-induced neointimal hyperplasia via the inhibition of VSMC migration, without inducing apoptosis or cell cycle arrest. General Significance We propose morelloflavone to be a viable oral agent for the prevention of restenosis, without compromising effects on the integrity and healing of the injured arteries.

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“…Both of these drugs are believed to work by inhibiting smooth-muscle-cell proliferation and cell-matrix synthesis. 10,15 Paclitaxel…”

Section: Rationale For Drug-eluting Stentsmentioning

confidence: 99%

Paclitaxel-eluting stents in coronary artery disease

Nawarskas

Osborn

2005

American Journal of Health-System Pharmacy

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The Effects of Paclitaxel on the Three Phases of Restenosis

Abstract: Paclitaxel is a potent inhibitor of SMC proliferation, SMC migration, and extracellular matrix formation in vitro, with all three phases of the restenosis process inhibited effectively.

Cited by 57 publications

References 41 publications

Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement

Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement

Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration

Paclitaxel-eluting stents in coronary artery disease

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