Abstract
The implantation of coronary stents for coronary artery diseases is one of the most common percutaneous procedures. Among them, drug-eluting stents have been widely used for more than 3 years to overcome in-stent restenosis (ISR), the Achilles heel of angioplasty. Numerous trials have shown the remarkable efficiency of rapamycin (sirolimus)- eluting stents for the prevention of ISR. ISR is mostly due to hyperplasia of smooth muscle cells in the intimal layer of the vessel wall (so-called neointima hyperplasia). The cellular mechanism of rapamycin is mediated by binding to the FK506 binding protein, followed by inhibiting a kinase known as the target of rapamycin. Cell cycle genes and their products, such as cyclin, cyclin dependent kinases (Cdks), and Cdk inhibitors (CKIs), are the molecules to conserve the cell cycle progression and checkpoint traverse. While Cdks act as an accelerator, CKIs are brakes for cell cycle and these molecules affect each other. Inhibiting the target of rapamycin results in an elevation of CKI, p27Kip1. This inhibition possesses antiproliferative effects on smooth muscle cells by blocking cell-cycle progression at the G1/S transition. This review will focus on the current status of our knowledge regarding rapamycin in the era of the drug-eluting stent.
Keywords: Rapamycin, cell cycle, in-stent restenosis, drug-eluting stent
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