Sirolimus- and taxol-eluting stents differ towards intimal hyperplasia and re-endothelialization.
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.
Liuzzo
John P
JP
Department of Medicine, Saint Vincent Catholic Medical Center, Comprehensive Cardiovascular Center Research Office, Cronin Building, Room 990, 170 West 12 Street, New York, New York 10011, USA. jliu2006@yahoo.com
Ambrose
John A
JA
Coppola
John T
JT
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D020099:Coated Materials, Biocompatible; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D011474:Prosthesis Design; D020123:Sirolimus / Q000494:pharmacology*; D015607:Stents; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D020099:Coated Materials, Biocompatible; D007166:Immunosuppressive Agents; D017239:Paclitaxel; D020123:Sirolimus