Sirolimus- and Taxol-eluting Stents Differ Towards Hyperplasia
Restenosis is a direct result of vessel injury, local inflammation, and remodeling following balloon angioplasty and coronary stenting resulting in luminal narrowing. The process involves a complex interplay of released growth factors that stimulate smooth muscle cells (SMCs) to migrate and proliferate, as well as activating endothelial cells (ECs) at injury sites. The latter re-establishes the luminal endothelial monolayer that keeps a barrier to circulating cells from underlying extracellular matrix and SMCs. Understanding the cellular mechanisms of intimal hyperplasia and re-endothelialization is important in that uncontrolled cellular processes account for coronary luminal narrowing, leading to the recurrence of clinical symptoms, hospitalizations, and repeat interventions. The evolution of drug-eluting stents that inhibit intimal hyperplasia has revolutionized percutaneous coronary interventions in that potential late luminal narrowing is attenuated. Sirolimus and paclitaxel are two medications utilized for their efficacy at inhibiting intimal hyperplasia and subsequent clinical events. The effects of these drugs on EC biology have not been well investigated. This article discusses basic cellular processes of vessel repair after balloon angioplasty and stenting, and focuses on the differential molecular mechanisms of sirolimus and paclitaxel towards proliferation and migration. These drugs inhibit both SMC and EC proliferation, but by different mechanisms, and paclitaxel inhibits EC migration, whereas sirolimus does not. Their discriminating effects towards re-endothelialization may clinically differentiate these two drugs. Inhibiting re-endothelialization may translate into more adverse clinical events.
In-stent restenosis of coronary arteries is the major reason for the recurrence of occlusion after successful percutaneous coronary intervention (PCI) and occurs in 20–50% of patients. The development of in-stent restenosis depends on complex cellular interactions within the vessel wall involving endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, lymphocytes, and macrophages. Vessel injury from balloon angioplasty and stenting cause the release of soluble mediators that initiate cellular activation, migration, proliferation, extracellular matrix production and secretion via autocrine or paracrine mechanisms. The recent development of intracoronary stents coated with drugs that inhibit in-stent restenosis rely on the fact that cell proliferation and cell migration play key roles in this process. Sirolimus- (Rapamune,Wyeth Ayerst Laboratories, Madison, New Jersey) eluting stents (Cordis Corporation, Johnson & Johnson, Miami, Florida), and paclitaxel- (Taxol, Bristol Myers Squibb Company, Princeton, New Jersey) eluting stents (Boston Scientific Corporation, Maple Grove, Minnesota) are clinically effective inhibitors of in-stent restenosis when utilized with concomitant antiplatelet therapy. This article focuses on how the molecular mechanisms of these two drug-eluting stents differ specifically in their course of action towards ECs and SMCs. Much of the data available are derived from cellular studies and animal models and are translated to humans since it has been difficult to study these cellular processes in vivo in humans.
Restenosis is a direct result of vessel injury, local inflammation, and remodeling following balloon angioplasty and coronary stenting resulting in luminal narrowing. The process involves a complex interplay of released growth factors that stimulate smooth muscle cells (SMCs) to migrate and proliferate, as well as activating endothelial cells (ECs) at injury sites. The latter re-establishes the luminal endothelial monolayer that keeps a barrier to circulating cells from underlying extracellular matrix and SMCs. Understanding the cellular mechanisms of intimal hyperplasia and re-endothelialization is important in that uncontrolled cellular processes account for coronary luminal narrowing, leading to the recurrence of clinical symptoms, hospitalizations, and repeat interventions. The evolution of drug-eluting stents that inhibit intimal hyperplasia has revolutionized percutaneous coronary interventions in that potential late luminal narrowing is attenuated. Sirolimus and paclitaxel are two medications utilized for their efficacy at inhibiting intimal hyperplasia and subsequent clinical events. The effects of these drugs on EC biology have not been well investigated. This article discusses basic cellular processes of vessel repair after balloon angioplasty and stenting, and focuses on the differential molecular mechanisms of sirolimus and paclitaxel towards proliferation and migration. These drugs inhibit both SMC and EC proliferation, but by different mechanisms, and paclitaxel inhibits EC migration, whereas sirolimus does not. Their discriminating effects towards re-endothelialization may clinically differentiate these two drugs. Inhibiting re-endothelialization may translate into more adverse clinical events.
In-stent restenosis of coronary arteries is the major reason for the recurrence of occlusion after successful percutaneous coronary intervention (PCI) and occurs in 20–50% of patients. The development of in-stent restenosis depends on complex cellular interactions within the vessel wall involving endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, lymphocytes, and macrophages. Vessel injury from balloon angioplasty and stenting cause the release of soluble mediators that initiate cellular activation, migration, proliferation, extracellular matrix production and secretion via autocrine or paracrine mechanisms. The recent development of intracoronary stents coated with drugs that inhibit in-stent restenosis rely on the fact that cell proliferation and cell migration play key roles in this process. Sirolimus- (Rapamune,Wyeth Ayerst Laboratories, Madison, New Jersey) eluting stents (Cordis Corporation, Johnson & Johnson, Miami, Florida), and paclitaxel- (Taxol, Bristol Myers Squibb Company, Princeton, New Jersey) eluting stents (Boston Scientific Corporation, Maple Grove, Minnesota) are clinically effective inhibitors of in-stent restenosis when utilized with concomitant antiplatelet therapy. This article focuses on how the molecular mechanisms of these two drug-eluting stents differ specifically in their course of action towards ECs and SMCs. Much of the data available are derived from cellular studies and animal models and are translated to humans since it has been difficult to study these cellular processes in vivo in humans.
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